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Sample records for ad postmortem brains

  1. Protein phosphorylation systems in postmortem human brain

    SciTech Connect

    Walaas, S.I.; Perdahl-Wallace, E.; Winblad, B.; Greengard, P. )

    1989-01-01

    Protein phosphorylation systems regulated by cyclic adenosine 3',5'-monophosphate (cyclic AMP), or calcium in conjunction with calmodulin or phospholipid/diacylglycerol, have been studied by phosphorylation in vitro of particulate and soluble fractions from human postmortem brain samples. One-dimensional or two-dimensional gel electrophoretic protein separations were used for analysis. Protein phosphorylation catalyzed by cyclic AMP-dependent protein kinase was found to be highly active in both particulate and soluble preparations throughout the human CNS, with groups of both widely distributed and region-specific substrates being observed in different brain nuclei. Dopamine-innervated parts of the basal ganglia and cerebral cortex contained the phosphoproteins previously observed in rodent basal ganglia. In contrast, calcium/phospholipid-dependent and calcium/calmodulin-dependent protein phosphorylation systems were less prominent in human postmortem brain than in rodent brain, and only a few widely distributed substrates for these protein kinases were found. Protein staining indicated that postmortem proteolysis, particularly of high-molecular-mass proteins, was prominent in deeply located, subcortical regions in the human brain. Our results indicate that it is feasible to use human postmortem brain samples, when obtained under carefully controlled conditions, for qualitative studies on brain protein phosphorylation. Such studies should be of value in studies on human neurological and/or psychiatric disorders.

  2. Mitochondrial viability in mouse and human postmortem brain

    PubMed Central

    Barksdale, Keri A.; Perez-Costas, Emma; Gandy, Johanna C.; Melendez-Ferro, Miguel; Roberts, Rosalinda C.; Bijur, Gautam N.

    2010-01-01

    Neuronal function in the brain requires energy in the form of ATP, and mitochondria are canonically associated with ATP production in neurons. The electrochemical gradient, which underlies the mitochondrial transmembrane potential (ΔΨmem), is harnessed for ATP generation. Here we show that ΔΨmem and ATP-production can be engaged in mitochondria isolated from human brains up to 8.5 h postmortem. Also, a time course of postmortem intervals from 0 to 24 h using mitochondria isolated from mouse cortex reveals that ΔΨmem in mitochondria can be reconstituted beyond 10 h postmortem. It was found that complex I of the mitochondrial electron transport chain was affected adversely with increasing postmortem intervals. Mitochondria isolated from postmortem mouse brains maintain the ability to produce ATP, but rates of production decreased with longer postmortem intervals. Furthermore, we show that postmortem brain mitochondria retain their ΔΨmem and ATP-production capacities following cryopreservation. Our finding that ΔΨmem and ATP-generating capacity can be reinitiated in brain mitochondria hours after death indicates that human postmortem brains can be an abundant source of viable mitochondria to study metabolic processes in health and disease. It is also possible to archive these mitochondria for future studies.—Barksdale, K. A., Perez-Costas, E., Gandy, J. C., Melendez-Ferro, M., Roberts, R. C., Bijur, G. N. Mitochondrial viability in mouse and human postmortem brain. PMID:20466876

  3. Postmortem Brain: An Underutilized Substrate for Studying Severe Mental Illness

    PubMed Central

    McCullumsmith, Robert E; Hammond, John H; Shan, Dan; Meador-Woodruff, James H

    2014-01-01

    We propose that postmortem tissue is an underutilized substrate that may be used to translate genetic and/or preclinical studies, particularly for neuropsychiatric illnesses with complex etiologies. Postmortem brain tissues from subjects with schizophrenia have been extensively studied, and thus serve as a useful vehicle for illustrating the challenges associated with this biological substrate. Schizophrenia is likely caused by a combination of genetic risk and environmental factors that combine to create a disease phenotype that is typically not apparent until late adolescence. The complexity of this illness creates challenges for hypothesis testing aimed at understanding the pathophysiology of the illness, as postmortem brain tissues collected from individuals with schizophrenia reflect neuroplastic changes from a lifetime of severe mental illness, as well as treatment with antipsychotic medications. While there are significant challenges with studying postmortem brain, such as the postmortem interval, it confers a translational element that is difficult to recapitulate in animal models. On the other hand, data derived from animal models typically provide specific mechanistic and behavioral measures that cannot be generated using human subjects. Convergence of these two approaches has led to important insights for understanding molecular deficits and their causes in this illness. In this review, we discuss the problem of schizophrenia, review the common challenges related to postmortem studies, discuss the application of biochemical approaches to this substrate, and present examples of postmortem schizophrenia studies that illustrate the role of the postmortem approach for generating important new leads for understanding the pathophysiology of severe mental illness. PMID:24091486

  4. Freezing effect on brain density in postmortem CT.

    PubMed

    Sugimoto, Miyu; Hyodoh, Hideki; Rokukawa, Masumi; Kanazawa, Ayumi; Murakami, Rina; Shimizu, Junya; Okazaki, Shunichiro; Mizuo, Keisuke; Watanabe, Satoshi

    2016-01-01

    Two 60-year-old males were found at their homes whose bodies had deteriorated due to putrefaction. To prevent worm invasion and minimize deterioration, dry ice was used prior to the autopsy investigation. Prior to autopsy, postmortem CT demonstrated a decreased density in brain parenchyma at the dry-iced side, and autopsy revealed deteriorated brain parenchyma with frozen effect (presented like sherbet). Moreover, the deteriorated cerebral parenchyma maintained their structure and they were evaluated by cutting. When lower CT density presents in postmortem CT, the freezing effect may need to be considered and the physician should evaluate the cadaver's postmortem condition to prevent misdiagnoses. PMID:26832379

  5. Postmortem Quetiapine Reference Concentrations in Brain and Blood.

    PubMed

    Skov, Louise; Johansen, Sys Stybe; Linnet, Kristian

    2015-09-01

    Brain tissue is a useful alternative to blood in postmortem forensic investigations, but scarcity of information on reference concentrations in brain tissue makes interpretation challenging. Here we present a study of 43 cases where the antipsychotic drug quetiapine was quantified in brain tissue and related to concentrations in postmortem blood. For cases, where quetiapine was unrelated to the cause of death (N = 36), the 10-90 percentiles for quetiapine concentrations in brain tissue were 0.030-1.54 mg/kg (median 0.48 mg/kg, mean 0.79 mg/kg). Corresponding blood 10-90 percentile values were 0.007-0.39 mg/kg (median 0.15 mg/kg, mean 0.19 mg/kg), giving brain-blood ratio 10-90 percentiles of 2.31-6.54 (median 3.87, mean 4.32). Both correspond well to the limited amount of data found in the literature. For cases where quetiapine was a contributing factor to death (N = 5), the median value in brain tissue of 8.02 mg/kg (range 2.69-22.98 mg/kg) was more than 15 times higher than the median of the nontoxic values, and about the same relationship occurred for blood with a median of 3.19 mg/kg (range 1.00-6.90 mg/kg). The brain-blood ratios for toxic concentrations were in the range of 2.08-6.05, which correspond to those of the nontoxic concentrations. A single case, where quetiapine was ruled as the sole cause of death, a suicide by quetiapine overdose, had an even higher value of 25.74 mg/kg in brain tissue. The blood concentration was 8.99 mg/kg, giving a brain-blood ratio of 2.86. Thus, on average the brain concentrations were about four times the blood concentrations. The brain concentrations of quetiapine observed in cases, where quetiapine was unrelated to death, may serve as a reference, when evaluating postmortem cases with no blood available. The recorded concentrations, where quetiapine was contributing to death, give an indication of likely toxic concentrations. PMID:26159868

  6. Tourette's syndrome: a neurochemical analysis of postmortem cortical brain tissue.

    PubMed

    Singer, H S; Hahn, I H; Krowiak, E; Nelson, E; Moran, T

    1990-04-01

    Postmortem frontal, temporal, and occipital regions of the brain from adult patients who had a diagnosis of Tourette's syndrome were analyzed for neurochemical alterations. In 3 of 4 TS-affected brains, the concentration of adenosine 3',5'-monophosphate (cyclic AMP) was reduced in all brain regions evaluated. This diminution in cyclic AMP was not associated with a significant change in the activity of the synthesizing enzyme, adenylate cyclase. No significant differences were identified for the neurotransmitter-synthesizing enzymes choline acetyltransferase and glutamate decarboxylase. Concentrations of dopamine, norepinephrine, and the serotonin metabolite 5-hydroxyindoleacetic acid were not altered. Postsynaptic receptor-binding activity for muscarinic cholinergic ([3H]quinuclidinyl benzilate) and beta receptors ([125I]iodocyanopindolol) showed no generalized impairment. It is suggested that symptoms of Tourette's syndrome might be related to an abnormality within a second messenger system. PMID:1972320

  7. Analysis of RNA from Alzheimer's Disease Post-mortem Brain Tissues.

    PubMed

    Clement, Christian; Hill, James M; Dua, Prerna; Culicchia, Frank; Lukiw, Walter J

    2016-03-01

    Alzheimer's disease (AD) is a uniquely human, age-related central nervous system (CNS) disorder for which there is no adequate experimental model. While well over 100 transgenic murine models of AD (TgAD) have been developed that recapitulate many of the neuropathological features of AD, key pathological features of AD such as progressive neuronal atrophy, neuron cell loss, and neurofibrillary tangle (NFT) formation have not been observed in any TgAD model to date. To more completely analyze and understand the neuropathology, altered neuro-inflammatory and innate-immune signaling pathways, and the complex molecular-genetics and epigenetics of AD, it is therefore necessary to rigorously examine short post-mortem interval (PMI) human brain tissues to gain a deeper and more thorough insight into the neuropathological mechanisms that characterize the AD process. This perspective-methods paper will highlight some important recent findings on the utilization of short PMI tissues in sporadic (idiopathic; of unknown origin) AD research with focus on the extraction and quantification of RNA, and in particular microRNA (miRNA) and messenger RNA (mRNA) and analytical strategies, drawing on the authors' combined 125 years of laboratory experience into this investigative research area. We sincerely hope that new investigators in the field of "gene expression analysis in neurological disease" will benefit from the observations presented here and incorporate these recent findings and observations into their future experimental planning and design. PMID:25631714

  8. Limited predictability of postmortem human brain tissue quality by RNA integrity numbers.

    PubMed

    Sonntag, Kai-C; Tejada, George; Subburaju, Sivan; Berretta, Sabina; Benes, Francine M; Woo, Tsung-Ung W

    2016-07-01

    The RNA integrity number (RIN) is often considered to be a critical measure of the quality of postmortem human brains. However, it has been suggested that RINs do not necessarily reflect the availability of intact mRNA. Using the Agilent bioanalyzer and qRT-PCR, we explored whether RINs provide a meaningful way of assessing mRNA degradation and integrity in human brain samples by evaluating the expression of 3'-5' mRNA sequences of the cytochrome C-1 (CYC1) gene. Analysis of electropherograms showed that RINs were not consistently correlated with RNA or cDNA profiles and appeared to be poor predictors of overall cDNA quality. Cycle thresholds from qRT-PCR analysis to quantify the amount of CYC1 mRNA revealed positive correlations of RINs with amplification of full-length transcripts, despite the variable degree of linear degradation along the 3'-5' sequence. These data demonstrate that in postmortem human brain tissue the RIN is an indicator of mRNA quantity independent of degradation, but does not predict mRNA integrity, suggesting that RINs provide an incomplete measure of brain tissue quality. Quality assessment of postmortem human brains by RNA integrity numbers (RINs) may be misleading, as they do not measure intact mRNAs. We show that the RIN is an indicator of mRNA quantity independent of degradation, but does not predict mRNA integrity, suggesting that RINs provide an incomplete measure of brain tissue quality. Our results resolve controversial assumption on interpreting quality assessments of human postmortem brains by RINs. PMID:27062510

  9. Postmortem MRI of Human Brain Hemispheres: T2 Relaxation Times during Formaldehyde Fixation

    PubMed Central

    Dawe, Robert J.; Bennett, David A.; Schneider, Julie A.; Vasireddi, Sunil K.; Arfanakis, Konstantinos

    2009-01-01

    Unlike in vivo imaging, postmortem MRI allows for invasive examination of the tissue specimen immediately following the MR scan. However, natural tissue decomposition and chemical fixation cause the postmortem tissue’s MRI properties to be different from those found in vivo. Moreover, these properties change as postmortem fixation time elapses. The goal of this study was to characterize the T2 relaxation changes that occur over time in cadaveric human brain hemispheres during fixation. Five hemispheres immersed in formaldehyde solution were scanned on a weekly basis for three months postmortem, and once again at six months postmortem. The T2 relaxation times were measured throughout the hemispheres. Over time, T2 values near the edges of the hemispheres decreased rapidly after death, while T2 values of deep tissue decreased more slowly. This difference is likely due to the relatively large distance from the hemisphere surface, and other barriers limiting diffusion of formaldehyde molecules to deep tissues. In addition, T2 values in deep tissue did not continuously decay to a plateau, but instead reached a minimum and then increased to a plateau. This final increase may be due to the effects of prolonged tissue decomposition, a hypothesis that is supported by numerical simulations of the fixation process. PMID:19189294

  10. Postmortem Brain and Blood Reference Concentrations of Alprazolam, Bromazepam, Chlordiazepoxide, Diazepam, and their Metabolites and a Review of the Literature.

    PubMed

    Skov, Louise; Holm, Karen Marie Dollerup; Johansen, Sys Stybe; Linnet, Kristian

    2016-09-01

    To interpret postmortem toxicology results, reference concentrations for non-toxic and toxic levels are needed. Usually, measurements are performed in blood, but because of postmortem redistribution phenomena this may not be optimal. Rather, measurement in the target organ of psychoactive drugs, the brain, might be considered. Here we present reference concentrations of femoral blood and brain tissue of selected benzodiazepines (BZDs). Using LC-MS/MS, we quantified alprazolam, bromazepam, chlordiazepoxide, diazepam, and the metabolites desmethyldiazepam, oxazepam and temazepam in postmortem femoral blood and brain tissue in 104 cases. BZDs were judged to be unrelated to the cause of death in 88 cases and contributing to death in 16 cases. No cases were found with cause of death solely attributed to BZD poisoning. All BZDs investigated tended to have higher concentrations in brain than in blood with median brain-blood ratios ranging from 1.1 to 2.3. A positive correlation between brain and blood concentrations was found with R(2) values from 0.51 to 0.95. Our reported femoral blood concentrations concur with literature values, but sparse information on brain concentration was available. Drug-metabolite ratios were similar in brain and blood for most compounds. Duplicate measurements of brain samples showed that the pre-analytical variation in brain (5.9%) was relatively low, supporting the notion that brain tissue is a suitable postmortem specimen. The reported concentrations in both brain and blood can be used as reference values when evaluating postmortem cases. PMID:27416838

  11. Postmortem changes in the neuroanatomical characteristics of the primate brain: hippocampal formation.

    PubMed

    Lavenex, Pierre; Lavenex, Pamela Banta; Bennett, Jeffrey L; Amaral, David G

    2009-01-01

    Comparative studies of the structural organization of the brain are fundamental to our understanding of human brain function. However, whereas brains of experimental animals are fixed by perfusion of a fixative through the vasculature, human or ape brains are fixed by immersion after varying postmortem intervals. Although differential treatments might affect the fundamental characteristics of the tissue, this question has not been evaluated empirically in primate brains. Monkey brains were either perfused or acquired after varying postmortem intervals before immersion-fixation in 4% paraformaldehyde. We found that the fixation method affected the neuroanatomical characteristics of the monkey hippocampal formation. Soma size was smaller in Nissl-stained, immersion-fixed tissue, although overall brain volume was larger as compared to perfusion-fixed tissue. Nonphosphorylated high-molecular-weight neurofilament immunoreactivity was lower in CA3 pyramidal neurons, dentate mossy cells, and the entorhinal cortex, whereas it was higher in the mossy fiber pathway in immersion-fixed tissue. Serotonin-immunoreactive fibers were well stained in perfused tissue but were undetectable in immersion-fixed tissue. Although regional immunoreactivity patterns for calcium-binding proteins were not affected, intracellular staining degraded with increasing postmortem intervals. Somatostatin-immunoreactive clusters of large axonal varicosities, previously reported only in humans, were observed in immersion-fixed monkey tissue. In addition, calretinin-immunoreactive multipolar neurons, previously observed only in rodents, were found in the rostral dentate gyrus in both perfused and immersion-fixed brains. In conclusion, comparative studies of the brain must evaluate the effects of fixation on the staining pattern of each marker in every structure of interest before drawing conclusions about species differences. PMID:18972553

  12. Autoradiographic analysis of alpha 1-noradrenergic receptors in the human brain postmortem. Effect of suicide

    SciTech Connect

    Gross-Isseroff, R.; Dillon, K.A.; Fieldust, S.J.; Biegon, A. )

    1990-11-01

    In vitro quantitative autoradiography of alpha 1-noradrenergic receptors, using tritiated prazosin as a ligand, was performed on 24 human brains postmortem. Twelve brains were obtained from suicide victims and 12 from matched controls. We found significant lower binding to alpha 1 receptors in several brain regions of the suicide group as compared with matched controls. This decrease in receptor density was evident in portions of the prefrontal cortex, as well as the temporal cortex and in the caudate nucleus. Age, sex, presence of alcohol, and time of death to autopsy did not affect prazosin binding, in our sample, as measured by autoradiography.

  13. Persistent Angiogenesis in the Autism Brain: An Immunocytochemical Study of Postmortem Cortex, Brainstem and Cerebellum

    PubMed Central

    Saccomano, Z. T.; Alzoobaee, M. F.; Boldrini, M.; Whitaker-Azmitia, P. M.

    2016-01-01

    In the current work, we conducted an immunocytochemical search for markers of ongoing neurogenesis (e.g. nestin) in auditory cortex from postmortem sections of autism spectrum disorder (ASD) and age-matched control donors. We found nestin labeling in cells of the vascular system, indicating blood vessels plasticity. Evidence of angiogenesis was seen throughout superior temporal cortex (primary auditory cortex), fusiform cortex (face recognition center), pons/midbrain and cerebellum in postmortem brains from ASD patients but not control brains. We found significant increases in both nestin and CD34, which are markers of angiogenesis localized to pericyte cells and endothelial cells, respectively. This labeling profile is indicative of splitting (intussusceptive), rather than sprouting, angiogenesis indicating the blood vessels are in constant flux rather than continually expanding. PMID:26667147

  14. Brain Fluid Content Related to Body Position and Postmortem Interval - An Animal Model.

    PubMed

    Leonard, Anna; Vink, Robert; Byard, Roger W

    2016-05-01

    Adult male Sprague Dawley rats were euthanized and placed in a horizontal or vertical (head-down) position at room temperature, after which brain fluid content was measured by a moisture analysis technique at variable time points. No significant difference in brain fluid content was observed between horizontal and vertical postmortem positions. A significant increase in brain fluid content was demonstrated 3, 6, and 24 h after death, with maximal fluid content observed at 24 h. Specifically, the brain fluid content of control animals was 77.79 ± 0.36%, increasing to 80.05 ± 0.22% at 24 h (p < 0.0001). This study has demonstrated no significant differences in brain fluid content related to postmortem position, suggesting that a head-down position is not associated with increased brain fluid content or swelling. However, significant temporal increases in brain fluid content after death, most likely related to cerebral liquefaction, occur. PMID:27122403

  15. Postmortem changes in rat brain: studies on membrane-bound enzymes and receptors.

    PubMed

    Syapin, P J; Ritchie, T; Noble, L; Noble, E P

    1987-04-01

    The relationship between the stability of potential neurochemical markers and autolysis time was studied at 4 degrees C and 25 degrees C using postmortem brain samples from two rat strains. In general, qualitatively similar results were obtained with either N/Nih or Sprague-Dawley rats; however, quantitative differences were often observed, particularly in regard to benzodiazepine receptor changes. For every enzyme activity or binding property examined, no significant change was found when brains were kept at 4 degrees C for up to 72 h prior to freezing at -70 degrees C. Na,K-ATPase and low-affinity Ca-ATPase activities were also stable in brains kept at 25 degrees C for up to 72 h. Mg-ATPase activity was reduced in brains kept at 25 degrees C for 24 and 48 h. [3H]Guanidinoethylmercaptosuccinic acid [( 3H]GEMSA) binding to enkephalin convertase in the cytosol was not significantly changed in brains kept at 25 degrees C; however, a small increase was seen for [3H]GEMSA binding to the membrane fraction at 24, but not 48 and 72 h postmortem. [3H]Quinuclidinyl benzilate [( 3H]QNB) binding to muscarinic cholinergic receptors decreased in brains kept at 25 degrees C for 72 h. Opioid receptor binding also decreased in brains kept at 25 degrees C. Using [3H]2-D-alanine-5-D-leucine enkephalin to label delta opioid receptors, a statistically significant decrease in binding was observed as early as 6 h postmortem, and was completely abolished after 72 h at 25 degrees C. In contrast, [3H]naloxone binding was unchanged after 24 h at 25 degrees C, but was decreased after 48 and 72 h.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:3029332

  16. Post-mortem 1.5T MR quantification of regular anatomical brain structures.

    PubMed

    Zech, Wolf-Dieter; Hottinger, Anna-Lena; Schwendener, Nicole; Schuster, Frederick; Persson, Anders; Warntjes, Marcel J; Jackowski, Christian

    2016-07-01

    Recently, post-mortem MR quantification has been introduced to the field of post-mortem magnetic resonance imaging. By usage of a particular MR quantification sequence, T1 and T2 relaxation times and proton density (PD) of tissues and organs can be quantified simultaneously. The aim of the present basic research study was to assess the quantitative T1, T2, and PD values of regular anatomical brain structures for a 1.5T application and to correlate the assessed values with corpse temperatures. In a prospective study, 30 forensic cases were MR-scanned with a quantification sequence prior to autopsy. Body temperature was assessed during MR scans. In synthetically calculated T1, T2, and PD-weighted images, quantitative T1, T2 (both in ms) and PD (in %) values of anatomical structures of cerebrum (Group 1: frontal gray matter, frontal white matter, thalamus, internal capsule, caudate nucleus, putamen, and globus pallidus) and brainstem/cerebellum (Group 2: cerebral crus, substantia nigra, red nucleus, pons, cerebellar hemisphere, and superior cerebellar peduncle) were assessed. The investigated brain structures of cerebrum and brainstem/cerebellum could be characterized and differentiated based on a combination of their quantitative T1, T2, and PD values. MANOVA testing verified significant differences between the investigated anatomical brain structures among each other in Group 1 and Group 2 based on their quantitative values. Temperature dependence was observed mainly for T1 values, which were slightly increasing with rising temperature in the investigated brain structures in both groups. The results provide a base for future computer-aided diagnosis of brain pathologies and lesions in post-mortem magnetic resonance imaging. PMID:26872469

  17. A diffusion tensor MRI atlas of the postmortem rhesus macaque brain.

    PubMed

    Calabrese, Evan; Badea, Alexandra; Coe, Christopher L; Lubach, Gabriele R; Shi, Yundi; Styner, Martin A; Johnson, G Allan

    2015-08-15

    The rhesus macaque (Macaca mulatta) is the most widely used nonhuman primate for modeling the structure and function of the brain. Brain atlases, and particularly those based on magnetic resonance imaging (MRI), have become important tools for understanding normal brain structure, and for identifying structural abnormalities resulting from disease states, exposures, and/or aging. Diffusion tensor imaging (DTI)-based MRI brain atlases are widely used in both human and macaque brain imaging studies because of the unique contrasts, quantitative diffusion metrics, and diffusion tractography that they can provide. Previous MRI and DTI atlases of the rhesus brain have been limited by low contrast and/or low spatial resolution imaging. Here we present a microscopic resolution MRI/DTI atlas of the rhesus brain based on 10 postmortem brain specimens. The atlas includes both structural MRI and DTI image data, a detailed three-dimensional segmentation of 241 anatomic structures, diffusion tractography, cortical thickness estimates, and maps of anatomic variability among atlas specimens. This atlas incorporates many useful features from previous work, including anatomic label nomenclature and ontology, data orientation, and stereotaxic reference frame, and further extends prior analyses with the inclusion of high-resolution multi-contrast image data. PMID:26037056

  18. Heparan sulfate deficiency in autistic postmortem brain tissue from the subventricular zone of the lateral ventricles

    PubMed Central

    Pearson, Brandon L.; Corley, Michael J.; Vasconcellos, Amy; Blanchard, D. Caroline; Blanchard, Robert J.

    2013-01-01

    Abnormal cellular growth and organization have been characterized in postmortem tissue from brains of autistic individuals, suggestive of pathology in a critical neurogenic niche, the subventricular zone (SVZ) of the brain lateral ventricles (LV). We examined cellular organization, cell proliferation, and constituents of the extracellular matrix such as N-sulfated heparan sulfate (HS) and laminin (LAM) in postmortem brain tissue from the LV-SVZ of young to elderly individuals with autism (n = 4) and age-matched typically developing (TD) individuals (n = 4) using immunofluorescence techniques. Strong and systematic reductions in HS immunofluorescence were observed in the LV-SVZ of the TD individuals with increasing age. For young through mature, but not elderly, autistic pair members, HS was reduced compared to their matched TDs. Cellular proliferation (Ki67+) was higher in the autistic individual of the youngest age-matched pair. These preliminary data suggesting that HS may be reduced in young to mature autistic individuals are in agreement with previous findings from the BTBR T+tf/J mouse, an animal model of autism; from mice with genetic modifications reducing HS; and with genetic variants in HS-related genes in autism. They suggest that aberrant extracellular matrix glycosaminoglycan function localized to the subventricular zone of the lateral ventricles may be a biomarker for autism, and potentially involved in the etiology of the disorder. PMID:23318464

  19. Increased steroid hormone dehydroepiandrosterone and pregnenolone levels in post-mortem brain samples of alcoholics.

    PubMed

    Kärkkäinen, Olli; Häkkinen, Merja R; Auriola, Seppo; Kautiainen, Hannu; Tiihonen, Jari; Storvik, Markus

    2016-05-01

    Intra-tissue levels of steroid hormones (e.g., dehydroepiandrosterone [DHEA], pregnenolone [PREGN], and testosterone [T]) may influence the pathological changes seen in neurotransmitter systems of alcoholic brains. Our aim was to compare levels of these steroid hormones between the post-mortem brain samples of alcoholics and non-alcoholic controls. We studied steroid levels with quantitative liquid chromatography-tandem mass spectrometry (LC-MS/MS) in post-mortem brain samples of alcoholics (N = 14) and non-alcoholic controls (N = 10). Significant differences were observed between study groups in DHEA and PREGN levels (p values 0.0056 and 0.019, respectively), but not in T levels. Differences between the study groups were most prominent in the nucleus accumbens (NAC), anterior cingulate cortex (ACC), and anterior insula (AINS). DHEA levels were increased in most alcoholic subjects compared to controls. However, only a subgroup of alcoholics showed increased PREGN levels. Negative Spearman correlations between tissue levels of PREGN and previous reports of [(3)H]naloxone binding to μ-opioid receptors were observed in the AINS, ACC, NAC, and frontal cortex (R values between -0.6 and -0.8; p values ≤ 0.002), suggesting an association between the opioid system and brain PREGN levels. Although preliminary, and from relatively small diagnostic groups, these results show significantly increased levels of DHEA and PREGN in the brains of alcoholics, and could be associated with the pathology of alcoholism. PMID:27139239

  20. Brain banks: benefits, limitations and cautions concerning the use of post-mortem brain tissue for molecular studies.

    PubMed

    Ferrer, Isidre; Martinez, Anna; Boluda, Susana; Parchi, Piero; Barrachina, Marta

    2008-09-01

    Brain banks are facilities providing an interface between generous donation of nervous tissues and research laboratories devoted to increase our understanding of the diseases of the nervous system, discover new diagnostic targets, and develop new strategies. Considering this crucial role, it is important to learn about the suitabilities, limitations and proper handling of individual brain samples for particular studies. Several factors may interfere with preservation of DNA, RNA, proteins and lipids, and, therefore, special care must be taken first to detect sub-optimally preserved tissues and second to provide adequate material for each specific purpose. Basic aspects related with DNA, RNA and protein preservation include agonal state, post-mortem delay, temperature of storage and procedures of tissue preservation. Examination of DNA and RNA preservation is best done by using bioanalyzer technologies instead of less sensitive methods such as agarose gels. Adequate RNA preservation is mandatory in RNA microarray studies and adequate controls are necessary for proper PCR validation. Like for RNA, the preservation of proteins is not homogeneous since some molecules are more vulnerable than others. This aspect is crucial in the study of proteins including expression levels and possible post-translational modifications. Similarly, the reliability of functional and enzymatic studies in human post-mortem brain largely depends on protein preservation. Much less is known about other aspects, such as the effects of putative deleterious factors on epigenetic events such as methylation of CpGs in gene promoters, nucleosome preservation, histone modifications, and conservation of microRNA species. Most brains are appropriate for morphological approaches but not all brains are useful for certain biochemical and molecular studies. PMID:18543077

  1. Simulated surgical-type cerebral biopsies from post-mortem brains allows accurate neuropathological diagnoses in the majority of neurodegenerative disease groups

    PubMed Central

    2013-01-01

    Background In theory, cerebral biopsies could provide the diagnosis in a significant proportion of patients with neurodegenerative diseases, however, there are considerable ethical barriers. Previous series of cerebral biopsies have shown variable diagnostic accuracy but have understandably suffered because of lack of post-mortem tissue with which to compare the diagnosis. To determine the accuracy of such biopsies in neurodegenerative disease we took small biopsy-sized samples of predominantly fresh post-mortem brain tissue from frontal and temporal lobes in 62 cases. These were processed as for a biopsy and stained for H&E, p62, tau, Aβ, α-synuclein, and TDP-43. The sections were assessed blind by 3 neuropathologists and the results compared with the final post-mortem diagnosis. Results The agreement and sensitivity in most cases was good especially: controls; Alzheimer’s disease (AD); multiple system atrophy (MSA); frontotemporal lobar degeneration with TDP-43 positive inclusions and/or motor neurone disease (FTLD-TDP/MND); Huntington’s disease (HD); corticobasal degeneration (CBD) / microtubular associated protein tau mutation cases with CBD-like features (CBD/MAPT); and combined AD- Dementia with Lewy Bodies (AD-DLB) where the sensitivity on assessing both brain regions varied between 75-100%. There was poor sensitivity for progressive supranuclear palsy (PSP) and amyotrophic lateral sclerosis (ALS) (both 0%), but moderate sensitivity for pure DLB (60%). The temporal lobe assessment was marginally more accurate than the frontal lobe but these were only slightly worse than both combined. Conclusions The study shows that with certain caveats the cerebral biopsy in life should be a viable method of accurately diagnosing many neurodegenerative diseases. PMID:24252649

  2. Increased acetyl and total histone levels in post-mortem Alzheimer's disease brain.

    PubMed

    Narayan, Pritika J; Lill, Claire; Faull, Richard; Curtis, Maurice A; Dragunow, Mike

    2015-02-01

    Histone acetylation is an epigenetic modification that plays a critical role in chromatin remodelling and transcriptional regulation. There is increasing evidence that epigenetic modifications may become compromised in aging and increase susceptibility to the development of neurodegenerative disorders such as Alzheimer's disease. Immunohistochemical labelling of free-floating sections from the inferior temporal gyrus (Alzheimer's disease, n=14; control, n=17) and paraffin-embedded tissue microarrays containing tissue from the middle temporal gyrus (Alzheimer's disease, n=29; control, n=28) demonstrated that acetyl histone H3 and acetyl histone H4 levels, as well as total histone H3 and total histone H4 protein levels, were significantly increased in post-mortem Alzheimer's disease brain tissue compared to age- and sex-matched neurologically normal control brain tissue. Changes in acetyl histone levels were proportional to changes in total histone levels. The increase in acetyl histone H3 and H4 was observed in Neuronal N immunopositive pyramidal neurons in Alzheimer's disease brain. Using immunolabelling, histone markers correlated significantly with the level of glial fibrillary acidic protein and HLA-DP, -DQ and -DR immunopositive cells and with the pathological hallmarks of Alzheimer's disease (hyperphosphorylated tau load and β-amyloid plaques). Given that histone acetylation changes were correlated with changes in total histone protein, it was important to evaluate if protein degradation pathways may be compromised in Alzheimer's disease. Consequently, significant positive correlations were also found between ubiquitin load and histone modifications. The relationship between histone acetylation and ubiquitin levels was further investigated in an in vitro model of SK-N-SH cells treated with the proteasome inhibitor Mg132 and the histone deacetylase inhibitor valproic acid. In this model, compromised protein degradation caused by Mg132 lead to elevated histone

  3. Quantitative measurement of [Na+] and [K+] in postmortem human brain tissue indicates disturbances in subjects with Alzheimer's disease and dementia with Lewy bodies.

    PubMed

    Graham, Stewart F; Nasarauddin, Muhammad Bin; Carey, Manus; McGuinness, Bernadette; Holscher, Christian; Kehoe, Patrick G; Love, Seth; Passmore, Anthony P; Elliott, Christopher T; Meharg, Andrew; Green, Brian D

    2015-01-01

    Alzheimer's disease (AD) is associated with significant disturbances in the homeostasis of Na+ and K+ ions as well as reduced levels of Na+/K+ ATPase in the brain. This study used ICP-MS to accurately quantify Na+ and K+ concentrations in human postmortem brain tissue. We analyzed parietal cortex (Brodmann area 7) from 28 cognitively normal age-matched controls, 15 cases of moderate AD, 30 severe AD, and 15 dementia with Lewy bodies (DLB). Associations were investigated between [Na+] and [K+] and a number of variables including diagnosis, age, gender, Braak tangle stage, amyloid-β (Aβ) plaque load, tau load, frontal tissue pH, and APOE genotype. Brains from patients with severe AD had significantly higher (26%; p < 0.001) [Na+] (mean 65.43 ± standard error 2.91 mmol/kg) than controls, but the concentration was not significantly altered in moderate AD or DLB. [Na+] correlated positively with Braak stage (r = 0.45; p < 0.0001), indicating association with disease severity. [K+] in tissue was 10% lower (p < 0.05) in moderate AD than controls. However, [K+] in severe AD and DLB (40.97 ± 1.31 mmol/kg) was not significantly different from controls. There was a significant positive correlation between [K+] and Aβ plaque load (r = 0.46; p = 0.035), and frontal tissue pH (r = 0.35; p = 0.008). [Na+] was not associated with [K+] across the groups, and neither ion was associated with tau load or APOE genotype. We have demonstrated disturbances of both [Na+] and [K+] in relation to the severity of AD and markers of AD pathology, although it is possible that these relate to late-stage secondary manifestations of the disease pathology. PMID:25362038

  4. What happens in the leucotomised brain? A postmortem morphological study of brains from schizophrenic patients.

    PubMed Central

    Pakkenberg, B

    1989-01-01

    Volume measurements were carried out on 19 brains from leucotomised schizophrenic patients and 20 age- and sex-matched controls using a stereological method. The volume of the total fixed brain, hemispheres, cortex, white matter, and central grey matter were all significantly reduced compared with controls. White matter and central grey structures were significantly reduced compared with a group of non-leucotomised schizophrenic brains. No difference was found in the size of the lesions in patients who improved compared with the patients who remained unchanged and the outcome was unrelated to lesional asymmetry. Morphometric measurements were correlated to a number of clinical parameters. PMID:2703834

  5. Determination of antidepressants in human postmortem blood, brain tissue, and hair using gas chromatography-mass spectrometry.

    PubMed

    Wille, Sarah M R; De Letter, Els A; Piette, Michel H A; Van Overschelde, Lien K; Van Peteghem, Carlos H; Lambert, Willy E

    2009-11-01

    A gas chromatographic-mass spectrometric (GC-MS) method in positive ion chemical ionization mode in combination with a solid phase extraction was optimized for new-generation antidepressants and their metabolites in postmortem blood, brain tissue, and hair. Twelve antidepressants and their active metabolites (i.e., mirtazapine, viloxazine, venlafaxine, citalopram, mianserin, reboxetine, fluoxetine, fluvoxamine, sertraline, maprotiline, melitracen, paroxetine, desmethylfluoxetine, desmethylmianserin, desmethylmirtazapine, desmethylsertraline, desmethylmaprotiline, desmethylcitalopram, and didesmethylcitalopram) could be quantified. In this article, in addition to the validation of the GC-MS method, four postmortem cases are discussed to demonstrate the usefulness of the described method in forensic toxicology. In these cases, sertraline, fluoxetine, citalopram, and trazodone in combination with their active metabolites were quantified. Blood concentrations ranged from subtherapeutic to toxic concentrations, while brain to plasma ratios ranged from 0.8 to 17. Hair concentrations ranged from 0.4 to 2.5 ng/mg depending on the compound and hair segment. PMID:18839201

  6. Guanidino compound levels in blood, cerebrospinal fluid, and post-mortem brain material of patients with argininemia.

    PubMed

    Deignan, Joshua L; De Deyn, Peter P; Cederbaum, Stephen D; Fuchshuber, Arno; Roth, Bernhard; Gsell, Wieland; Marescau, Bart

    2010-01-01

    The paucity of hyperammonemic crises together with spasticity, only seen in human arginase I deficient patients and not in patients with other urea cycle disorders, forces a search for candidates other than ammonia to associate with the pathophysiology and symptomatology. Therefore, we determined arginine together with some catabolites of arginine in blood and cerebrospinal fluid of these patients as well as in extremely rare post-mortem brain material of two patients with argininemia. The levels of alpha-keto-delta-guanidinovaleric acid, argininic acid and alpha-N-acetylarginine correlate with the arginine levels in blood and cerebrospinal fluid of patients with imposed or spontaneous protein restriction. The levels in blood are higher than the upper limit of normal in all studied patients. In addition to the highly increased levels of these same compounds in blood of a child with argininemia, the increase of guanidinoacetic acid, 24h before death, is remarkable. However, the manifest increases of these studied catabolites of arginine are not seen in post-mortem brain material of the same pediatric patient. Otherwise a clear increase of guanidinoacetic acid in post-mortem brain material of an adult patient was shown. A similar, comparable increase of homoarginine in both studied post-mortem brain materials is observed. Therefore the study of the pathobiochemistry of arginine in argininemia must be completed in the future by the determination of the end catabolites of the nitric oxide and agmatine biosynthesis pathways in the knockouts as well as in the patients to evaluate their role, together with the here studied catabolites, as candidates for association with pathophysiology and symptomatology. PMID:20176499

  7. Postmortem Magnetic Resonance Imaging to Guide the Pathological Cut: Individualized, 3D-Printed Cutting Boxes for Fixed Brains

    PubMed Central

    Absinta, Martina; Nair, Govind; Filippi, Massimo; Ray-Chaudhury, Abhik; Reyes-Mantilla, Maria I.; Pardo, Carlos A.; Reich, Daniel S.

    2014-01-01

    Interfacing magnetic resonance imaging (MRI) and pathology is critically important for understanding the pathological basis of MRI signal changes in vivo and for clinicopathological correlations. Postmortem MRI is an intermediate step in this process; unfortunately, however, relating the data to standard pathological sections, which are relatively thick and often non-parallel, is both time consuming and insufficiently accurate. The aim of this project was to develop technology to integrate postmortem, high-resolution, whole-brain MRI into the planning and execution of the pathological analysis through precise localization of the target and coordinates of cut. Compared to standard pathological sectioning, the use of an individualized 3D-printed cutting-box, designed based on postmortem MRI of formalin-fixed whole brains, improved the speed, quality, and accuracy of radiological-pathological correlation and, specifically, the histopathological localization of imaging findings. The technology described herein is easily implemented, applicable to any brain disorder, and potentially extendable to other organs. From the point of view of the pathologist this technique can improve localization of small or subtle abnormalities, whereas from the point of view of the radiologist it has the potential to improve understanding of MRI signal changes observed in disease. PMID:25007244

  8. Whole-hemisphere autoradiography of 5-HT₁B receptor densities in postmortem alcoholic brains.

    PubMed

    Storvik, Markus; Häkkinen, Merja; Tupala, Erkki; Tiihonen, Jari

    2012-06-30

    The 5-HT(1B) receptor has been associated with alcohol dependence, impulsive or alcohol-related aggressive behavior, and anxiety. The aim of this study was to determine whether or not the 5-HT(1B) receptor density differs in brain samples from anxiety-prone Cloninger type 1 alcoholics and socially hostile, predominantly male, type 2 alcoholics, and controls. Whole-hemispheric 5-HT(1B) receptor density was measured in eight regions of postmortem brains from 17 alcoholics and 10 nonalcoholic controls by autoradiography with tritiated GR-125743 and unlabeled ketanserin to prevent 5-HT(1D) binding. The 5-HT(1B) receptor density was not altered significantly in any of the studied regions. However, some correlations were observed in types 1 and 2 alcoholics only. The 5-HT(1B) receptor density decreased with age in type 1 alcoholics only. There was a significant positive correlation between 5-HT(1B) receptor and serotonin transporter densities in the head of caudate of type 1 alcoholics only. There was a significant positive correlation between 5-HT(1B) receptor density and dopaminergic terminal density, as estimated by vesicular monoamine transporter 2 measurement in the nucleus accumbens of type 2 alcoholics only. There were no significant correlations between 5-HT(1B) receptor and dopamine transporter or dopamine D2/D3 receptor densities in any of the subject groups. In conclusion, these results do not indicate primary changes in 5-HT(1B) receptor densities among these alcoholics, although the data must be considered as preliminary. PMID:22804971

  9. Felbamate increases [3H]glycine binding in rat brain and sections of human postmortem brain.

    PubMed

    McCabe, R T; Sofia, R D; Layer, R T; Leiner, K A; Faull, R L; Narang, N; Wamsley, J K

    1998-08-01

    The anticonvulsant compound felbamate (2-phenyl-1,3-propanediol dicarbamate; FBM) appears to inhibit the function of the N-methyl-D-aspartate (NMDA) receptor complex through an interaction with the strychnine-insensitive glycine recognition site. Since we have demonstrated previously that FBM inhibits the binding of [3H]5, 7-dichlorokynurenic acid (DCKA), a competitive antagonist at the glycine site, we assessed the ability of FBM to modulate the binding of an agonist, [3H]glycine, to rat forebrain membranes and human brain sections. In contrast to its ability to inhibit [3H]5,7-DCKA binding, FBM increased [3H]glycine binding (20 nM; EC50 = 485 microM; Emax = 211% of control; nH = 1.8). FBM, but not carbamazepine, phenytoin, valproic acid or phenobarbital, also increased [3H]glycine binding (50 nM; EC50 = 142 microM; Emax = 157% of control; nH = 1.6) in human cortex sections. Autoradiographic analysis of human brain slices demonstrated that FBM produced the largest increases in [3H]glycine binding in the cortex, hippocampus and the parahippocampal gyrus. Because various ions can influence the binding of glycine-site ligands, we assessed their effects on FBM-modulation of [3H]glycine binding. FBM-enhanced [3H]glycine binding was attenuated by Zn++ and not inhibited by Mg++ in human brain. These results suggest that FBM increases [3H]glycine binding in a manner sensitive to ions which modulate the NMDA receptor. These data support the hypothesis that FBM produces anticonvulsant and neuroprotective effects by inhibiting NMDA receptor function, likely through an allosteric modulation of the glycine site. PMID:9694960

  10. Diagnostic yield and accuracy of postmortem cytological sampling from the brain surface of animals with neurological abnormalities.

    PubMed

    Wünsche, S; Rosati, M; Matiasek, K

    2016-05-01

    Clarification of central nervous system (CNS) disorders frequently requires pathological investigation via brain biopsy or postmortem examination. The use of cytology is usually restricted to diagnosis of mass lesions and septic meningitis. The value of brain cytology at postmortem examination has not been explored sufficiently. This study aimed to clarify the diagnostic value of meningeal imprint cytology at postmortem brain examination. Samples were taken from cerebrum and cerebellum and stained with the modified Wright stain and with haematoxylin-eosin. The slides were evaluated and findings were compared to brain histopathology with respect to resemblance, discrepancy and diagnostic validity. The study included 169 cases involving multiple animal species. Histopathology identified inflammatory disorders in 60/135 (44.4%) cases, neoplasia in 19/135 (14.1%) and non-infiltrative diseases in 56/135 (41.5%). Cytology revealed pathological changes in 79/135 (58.5%) of these cases. The histopathological diagnosis was reproduced in 57/135 (42.2%) cases, 43/57 (75.4%) of which were inflammatory. Non-diagnostic cases included 16/135 (11.9%) with sub-diagnostic cytological features and 3/135 (2.2%) with unclear phenomena. In 55/135 (40.7%) of brains with histological lesions, cytology proved inferior, providing negative results, including 40/55 (72.7%) cases with non-infiltrative diseases, 12/55 (21.8%) with inflammation and 3/55 (5.5%) with neoplasia. Conversely, 3/34 (8.8%) of controls showed cytological abnormalities. Cytological sampling from CNS adds to the sensitivity of neuropathological investigations, even if restricted to non-invasive surface imprints. The diagnostic accuracy exceeds 40%, with infiltrative diseases being five times more likely to be detected than non-infiltrative diseases. PMID:27009475

  11. Astrocyte pathology in major depressive disorder: insights from human postmortem brain tissue.

    PubMed

    Rajkowska, Grazyna; Stockmeier, Craig A

    2013-10-01

    The present paper reviews astrocyte pathology in major depressive disorder (MDD) and proposes that reductions in astrocytes and related markers are key features in the pathology of MDD. Astrocytes are the most numerous and versatile of all types of glial cells. They are crucial to the neuronal microenvironment by regulating glucose metabolism, neurotransmitter uptake (particularly for glutamate), synaptic development and maturation and the blood brain barrier. Pathology of astrocytes has been consistently noted in MDD as well as in rodent models of depressive-like behavior. This review summarizes evidence from human postmortem tissue showing alterations in the expression of protein and mRNA for astrocyte markers such as glial fibrillary acidic protein (GFAP), gap junction proteins (connexin 40 and 43), the water channel aquaporin-4 (AQP4), a calcium-binding protein S100B and glutamatergic markers including the excitatory amino acid transporters 1 and 2 (EAAT1, EAAT2) and glutamine synthetase. Moreover, preclinical studies are presented that demonstrate the involvement of GFAP and astrocytes in animal models of stress and depressive-like behavior and the influence of different classes of antidepressant medications on astrocytes. In light of the various astrocyte deficits noted in MDD, astrocytes may be novel targets for the action of antidepressant medications. Possible functional consequences of altered expression of astrocytic markers in MDD are also discussed. Finally, the unique pattern of cell pathology in MDD, characterized by prominent reductions in the density of astrocytes and in the expression of their markers without obvious neuronal loss, is contrasted with that found in other neuropsychiatric and neurodegenerative disorders. PMID:23469922

  12. Associations between in vivo neuroimaging and postmortem brain cytokine markers in a rodent model of Wernicke’s Encephalopathy

    PubMed Central

    Zahr, Natalie M; Alt, Carsten; Mayer, Dirk; Rohlfing, Torsten; Manning-Bog, Amy; Luong, Richard; Sullivan, Edith V; Pfefferbaum, Adolf

    2014-01-01

    Thiamine (vitamin B1) deficiency, associated with a variety of conditions, including chronic alcoholism and bariatric surgery for morbid obesity, can result in the neurological disorder Wernicke’s encephalopathy (WE). Recent work building upon early observations in animal models of thiamine deficiency has demonstrated an inflammatory component to the neuropathology observed in thiamine deficiency. The present, multilevel study including in vivo magnetic resonance imaging (MRI) and spectroscopy (MRS) and postmortem quantification of chemokine and cytokine proteins sought to determine whether a combination of these in vivo neuroimaging tools could be used to characterize an in vivo MR signature for neuroinflammation. Thiamine deficiency for 12 days was used to model neuroinflammation; glucose loading in thiamine deficiency was used to accelerate neurodegeneration. Among 38 animals with regional brain tissue assayed postmortem for cytokine/chemokine protein levels, three groups of rats (controls+glucose, n=6; pyrithiamine+saline, n=5; pyrithiamine+glucose, n=13) underwent MRI/MRS at baseline (time 1), after 12 days of treatment (time 2), and 3h after challenge (glucose or saline, time 3). In the thalamus of glucose-challenged, thiamine deficient animals, correlations between in vivo measures of pathology (lower levels of N-acetyle aspartate and higher levels of lactate) and postmortem levels of monocyte chemotactic protein-1 (MCP-1, also known as chemokine ligand 2, CCL2) support a role for this chemokine in thiamine deficiency-related neurodegeneration, but do not provide a unique in vivo signature for neuroinflammation. PMID:24973622

  13. Effect of antemortem and postmortem factors on ( sup 3 H)MK-801 binding in the human brain: Transient elevation during early childhood

    SciTech Connect

    Kornhuber, J.; Mack-Burkhardt, F.; Konradi, C.; Fritze, J.; Riederer, P. )

    1989-01-01

    The effect of a number of antemortem and postmortem factors on ({sup 3}H)MK-801 binding was investigated under equilibrium conditions in the frontal cortex of human brains of 38 controls. Binding values transiently increased during the early postnatal period reaching a maximum at the age of about 2 years. After age 10 years ({sup 3}H)MK-801 binding sites disappeared at 5.7% per decade. The storage time of brain tissue had a reducing effect on these binding sites. There was no effect of gender, brain weight or postmortem time interval and the binding sites were bilaterally symmetrically distributed in the frontal cortex.

  14. Decreased GABA(A) benzodiazepine binding site densities in postmortem brains of Cloninger type 1 and 2 alcoholics.

    PubMed

    Laukkanen, Virpi; Storvik, Markus; Häkkinen, Merja; Akamine, Yumiko; Tupala, Erkki; Virkkunen, Matti; Tiihonen, Jari

    2013-03-01

    Ethanol modulates the GABA(A) receptor to cause sedative, anxiolytic and hypnotic effects that are qualitatively similar to benzodiazepines and barbiturates. The aim of this study was to explore if GABA(A) receptor density is altered in post-mortem brains of anxiety-prone Cloninger type 1 and socially hostile type 2 alcoholic subtypes when compared to controls. The GABA(A) binding site density was measured by whole-hemisphere autoradiography with tritium labeled flunitrazepam ([(3)H]flunitrazepam) from 17 alcoholic (nine type 1, eight type 2) and 10 non-alcoholic post-mortem brains, using cold flumazepam as a competitive ligand. A total of eight specific brain areas were examined. Alcoholics displayed a significantly (p < 0.001, bootstrap type generalizing estimating equations model) reduced [(3)H]flunitrazepam binding site density when compared to controls. When localized, type 2 alcoholics displayed a significantly (p ≤ 0.05) reduced [(3)H]flunitrazepam binding site density in the internal globus pallidus, the gyrus dentatus and the hippocampus, whereas type 1 alcoholics differed from controls in the internal globus pallidus and the hippocampus. While previous reports have demonstrated significant alterations in dopaminergic and serotonergic receptors between type 1 and type 2 alcoholics among these same subjects, we observed no statistically significant difference in [(3)H]flunitrazepam binding site densities between the Cloninger type 1 and type 2 alcoholics. PMID:23332316

  15. Monoaminergic neurotransmitter alterations in postmortem brain regions of depressed and aggressive patients with Alzheimer's disease.

    PubMed

    Vermeiren, Yannick; Van Dam, Debby; Aerts, Tony; Engelborghs, Sebastiaan; De Deyn, Peter P

    2014-12-01

    Depression and aggression in Alzheimer's disease (AD) are 2 of the most severe and prominent neuropsychiatric symptoms (NPS). Altered monoaminergic neurotransmitter system functioning has been implicated in both NPS, although their neurochemical etiology remains to be elucidated. Left frozen hemispheres of 40 neuropathologically confirmed AD patients were regionally dissected. Dichotomization based on depression and aggression scores resulted in depressed/nondepressed (AD + D/AD - D) and aggressive/nonaggressive (AD + Agr/AD - Agr) groups. Concentrations of dopamine, serotonin (5-HT), (nor)epinephrine ((N)E), and respective metabolites were determined using reversed-phase high-performance liquid chromatography. Significantly lower 3-methoxy-4-hydroxyphenylglycol (MHPG) and higher homovanillic acid levels were observed in Brodmann area (BA) 9 and 10 of AD + D compared with AD - D. In AD + Agr, 5-hydroxy-3-indoleacetic acid (5-HIAA) levels in BA9, 5-HIAA to 5-HT ratios in BA11, and MHPG, NE, and 5-HIAA levels in the hippocampus were significantly decreased compared with AD - Agr. These findings indicate that brain region-specific altered monoamines and metabolites may contribute to the occurrence of depression and aggression in AD. PMID:24997673

  16. Persistent Angiogenesis in the Autism Brain: An Immunocytochemical Study of Postmortem Cortex, Brainstem and Cerebellum

    ERIC Educational Resources Information Center

    Azmitia, E. C.; Saccomano, Z. T.; Alzoobaee, M. F.; Boldrini, M.; Whitaker-Azmitia, P. M.

    2016-01-01

    In the current work, we conducted an immunocytochemical search for markers of ongoing neurogenesis (e.g. nestin) in auditory cortex from postmortem sections of autism spectrum disorder (ASD) and age-matched control donors. We found nestin labeling in cells of the vascular system, indicating blood vessels plasticity. Evidence of angiogenesis was…

  17. Correlation of amyloid PET ligand florbetapir F 18 (18F-AV-45) binding with β-amyloid aggregation and neuritic plaque deposition in postmortem brain tissue

    PubMed Central

    Choi, Seok Rye; Schneider, Julie A.; Bennett, David A.; Beach, Thomas G.; Bedell, Barry J.; Zehntner, Simone P.; Krautkramer, Michael; Kung, Hank F.; Skovronsky, Daniel M.; Hefti, Franz; Clark, Christopher M.

    2011-01-01

    Background Florbetapir F 18 (18F-AV-45) is a positron emission tomography (PET) imaging ligand for the detection of amyloid aggregation associated with Alzheimer’s disease. Earlier data showed that florbetapir F 18 binds with high affinity to β-amyloid plaques in human brain homogenates (Kd = 3.7 nM) and has favorable imaging pharmacokinetic properties, including rapid brain penetration and washout. The present study used human autopsy brain tissue to evaluate the correlation between in vitro florbetapir F 18 binding and β-amyloid density measured by established neuropathological methods. Methods The localization and density of florbetapir F 18 binding in frozen and formalin-fixed paraffin-embedded sections of postmortem brain tissue from 40 subjects with a varying degree of neurodegenerative pathology was assessed by standard florbetapir F 18 autoradiography and correlated with the localization and density of β-amyloid identified by silver staining, thioflavin S staining, and immunohistochemistry. Results There were strong quantitative correlations between florbetapir F 18 tissue binding and both β-amyloid plaques identified by light microscopy (sliver staining and thioflavin S fluorescence) and by immunohistochemical measurements of β-amyloid using three antibodies recognizing different epitopes of the β-amyloid peptide (Aβ). Florbetapir F 18 did not bind to neurofibrillary tangles. Conclusion Florbetapir F 18 selectively binds β-amyloid in human brain tissue. The binding intensity was quantitatively correlated with the density of β-amyloid plaques identified by standard neuropathological techniques and correlated with the density of Aβ measured by immunohistochemistry. Since β-amyloid plaques are a defining neuropathological feature for Alzheimer’s disease, these results support the use of florbetapir F 18 as an amyloid PET ligand to identify the presence of AD pathology in patients with signs and symptoms of progressive late-life cognitive

  18. A biomechanical evaluation of skull-brain surrogates to blunt high-rate impacts to postmortem human subjects.

    PubMed

    Raymond, David E; Bir, Cynthia A

    2015-03-01

    The field of forensic injury biomechanics is an emerging field. Biomechanically validated tools may assist interdisciplinary teams of investigators in assessing mechanisms of blunt head trauma resulting in skull fractures. The objective of this study is to assess the biofidelity of spherical, frangible skull-brain (SB) surrogates. Blunt impacts were conducted at 20 m/s, using an instrumented 103 g rigid impactor, to the temporo-parietal region of four defleshed cephalic postmortem human subjects (PMHS). Force-deformation response, fracture tolerance, and fracture patterns were recorded for comparison to spherical skull-brain surrogates. Three brain substitutes were assessed: 10% gelatin, lead shot with Styrofoam and water. Force-deformation response of the skull-brain surrogates was similar to defleshed PMHS up to the point of fracture; however, none of the surrogates fractured at tolerance levels comparable to the PMHS. Fracture patterns of the skull-brain surrogates were linear and radiating, while PMHS fractures were all depressed, comminuted. PMID:25572885

  19. A comparison of mitochondrial DNA isolation methods in frozen post-mortem human brain tissue--applications for studies of mitochondrial genetics in brain disorders.

    PubMed

    Devall, Matthew; Burrage, Joe; Caswell, Richard; Johnson, Matthew; Troakes, Claire; Al-Sarraj, Safa; Jeffries, Aaron R; Mill, Jonathan; Lunnon, Katie

    2015-10-01

    Given that many brain disorders are characterized by mitochondrial dysfunction, there is a growing interest in investigating genetic and epigenetic variation in mitochondrial DNA (mtDNA). One major caveat for such studies is the presence of nuclear-mitochondrial pseudogenes (NUMTs), which are regions of the mitochondrial genome that have been inserted into the nuclear genome over evolution and, if not accounted for, can confound genetic studies of mtDNA. Here we provide the first systematic comparison of methods for isolating mtDNA from frozen post-mortem human brain tissue. Our data show that a commercial method from Miltenyi Biotec, which magnetically isolates mitochondria using antibodies raised against the mitochondrial import receptor subunit TOM22, gives significant mtDNA enrichment and should be considered the method of choice for mtDNA studies in frozen brain tissue. PMID:26458552

  20. Divergent effects of postmortem ambient temperature on organophosphorus- and carbamate-inhibited brain cholinesterase activity in birds

    USGS Publications Warehouse

    Hill, E.F.

    1989-01-01

    Time- and temperature-dependent postmortem changes in inhibited brain cholinesterase (ChE) activity may confound diagnosis of field poisoning of wildlife by anticholinesterase pesticide. Carbamate-inhibited ChE activity may return to normal within 1 to 2 days of exposure of intact carcass to moderate ambient temperature (18-32C). Organophosphorus-inhibited ChE activity becomes more depressed over the same time. Uninhibited ChE activity was resilient to above freezing temperature to 32C for 1 day and 25C for 3 days. Carbamate- and organophosphorus-inhibited ChE can be separated by incubation of homogenate for 1 hour at physiological temperatures; carbamylated ChE can be readily reactivated while phosphorylated ChE cannot.

  1. Flow cytometry analysis of synaptosomes from post-mortem human brain reveals changes specific to Lewy Body and Alzheimer’s Disease

    PubMed Central

    Postupna, Nadia O.; Keene, C. Dirk; Latimer, Caitlin; Sherfield, Emily E.; Van Gelder, Rachel D.; Ojemann, Jeffrey G.; Montine, Thomas J.; Darvas, Martin

    2014-01-01

    Synaptic dysfunction is thought to play an important role in the pathophysiology of neurodegenerative diseases, such as Alzheimer’s disease (AD) and Lewy body disease (LBD). To improve our understanding of synaptic alterations in health and disease, we investigated synaptosomes prepared from post-mortem human cerebral cortex, putamen, and two regions of the caudate nucleus, dorso-lateral (DL) and ventro-medial (VM), regions commonly affected in AD and LBD. We observed that the fraction of synaptosomal particles with reactivity for dopamine transporter (DAT) was significantly reduced in the putamen and VM caudate of patients with neuropathological diagnosis of LBD. As expected, these differences also were reflected in direct measurements of dopamine (DA) and its metabolite, 3,4-dihydroxyphenylacetic acid (DOPAC), in caudate and putamen of LBD patients. The fraction of synaptosomal particles positive for amyloid β (Aβ) was significantly increased in frontal cortical samples of patients with the neuropathological diagnosis of severe AD, and was positively correlated with disease progression. We also prepared synaptosomes from the striatum of mice with severe loss of DA neurons (Slc6a3-DTR mice) and wild-type littermate controls. We observed dramatically reduced levels of DAT-positive synaptosomes in Slc6a3-DTR mice following exposure to diphtheria toxin (DT). Striatal levels of DA and DOPAC in Slc6a3-DTR mice also were reduced significantly following DT exposure. We conclude that flow cytometric analysis of synaptosomes prepared from human or mouse brain provides an opportunity to study expression of pathology-associated proteins and also the specific loss of dopaminergic nerve terminals. Hence, we believe it is a valid method to detect pathological changes at the level of the synapse in LBD as well as AD. PMID:25068655

  2. Simultaneous quantification of nicotine, opioids, cocaine, and metabolites in human fetal postmortem brain by liquid chromatography tandem mass spectrometry

    PubMed Central

    Shakleya, Diaa M.

    2011-01-01

    A validated method for simultaneous LCMSMS quantification of nicotine, cocaine, 6-acetylmorphine (6AM), codeine, and metabolites in 100 mg fetal human brain was developed and validated. After homogenization and solid-phase extraction, analytes were resolved on a Hydro-RP analytical column with gradient elution. Empirically determined linearity was from 5–5,000 pg/mg for cocaine and benzoylecgonine (BE), 25–5,000 pg/mg for cotinine, ecgonine methyl ester (EME) and 6AM, 50–5000 pg/mg for trans-3-hydroxycotinine (OH-cotinine) and codeine, and 250–5,000 pg/mg for nicotine. Potential endogenous and exogenous interferences were resolved. Intra- and inter-assay analytical recoveries were ≥92%, intra- and inter-day and total assay imprecision were ≤14% RSD and extraction efficiencies were ≥67.2% with ≤83% matrix effect. Method applicability was demonstrated with a postmortem fetal brain containing 40 pg/mg cotinine, 65 pg/mg OH-cotinine, 13 pg/mg cocaine, 34 pg/mg EME, and 525 pg/mg BE. This validated method is useful for determination of nicotine, opioid, and cocaine biomarkers in brain. PMID:19229524

  3. Network Topology Analysis of Post-Mortem Brain Microarrays Identifies More Alzheimer's Related Genes and MicroRNAs and Points to Novel Routes for Fighting with the Disease.

    PubMed

    Chandrasekaran, Sreedevi; Bonchev, Danail

    2016-01-01

    Network-based approaches are powerful and beneficial tools to study complex systems in their entirety, elucidating the essential factors that turn the multitude of individual elements into a functional system. In this study we used critical network topology descriptors and guilt-by-association rule to explore and understand the significant molecular players, drug targets and underlying biological mechanisms of Alzheimer's disease. Analyzing two post-mortem brain gene microarrays (GSE4757 and GSE28146) with Pathway Studio software package we constructed and analyzed a set of protein-protein interaction, as well as miRNA-target networks. In a 4-step procedure the expression datasets were normalized using Robust Multi-array Average approach, while the modulation of gene expression by the disease was statistically evaluated by the empirical Bayes method from the limma Bioconductor package. Representative set of 214 seed-genes (p<0.01) common for the three brain sections of the two microarrays was thus created. The Pathway Studio analysis of the networks built identified 15 new potential AD-related genes and 17 novel AD-involved microRNAs. Using KEGG pathways relevant in Alzheimer's disease we built an integrated mechanistic network from the interactions between the overlapping genes in these pathways. Routes of possible disease initiation process were thus revealed through the CD4, DCN, and IL8 extracellular ligands. DAVID and IPA enrichment analysis uncovered a number of deregulated biological processes and pathways including neuron projection/differentiation, aging, oxidative stress, chemokine/ neurotrophin signaling, long-term potentiation and others. The findings in this study offer information of interest for subsequent experimental studies. PMID:26784894

  4. Individual Case Analysis of Postmortem Interval Time on Brain Tissue Preservation

    PubMed Central

    Blair, Jeffrey A.; Wang, Chunyu; Hernandez, Damarys; Siedlak, Sandra L.; Rodgers, Mark S.; Achar, Rojan K.; Fahmy, Lara M.; Torres, Sandy L.; Petersen, Robert B.; Zhu, Xiongwei; Casadesus, Gemma; Lee, Hyoung-gon

    2016-01-01

    At autopsy, the time that has elapsed since the time of death is routinely documented and noted as the postmortem interval (PMI). The PMI of human tissue samples is a parameter often reported in research studies and comparable PMI is preferred when comparing different populations, i.e., disease versus control patients. In theory, a short PMI may alleviate non-experimental protein denaturation, enzyme activity, and other chemical changes such as the pH, which could affect protein and nucleic acid integrity. Previous studies have compared PMI en masse by looking at many different individual cases each with one unique PMI, which may be affected by individual variance. To overcome this obstacle, in this study human hippocampal segments from the same individuals were sampled at different time points after autopsy creating a series of PMIs for each case. Frozen and fixed tissue was then examined by Western blot, RT-PCR, and immunohistochemistry to evaluate the effect of extended PMI on proteins, nucleic acids, and tissue morphology. In our results, immunostaining profiles for most proteins remained unchanged even after PMI of over 50 h, yet by Western blot distinctive degradation patterns were observed in different protein species. Finally, RNA integrity was lower after extended PMI; however, RNA preservation was variable among cases suggesting antemortem factors may play a larger role than PMI in protein and nucleic acid integrity. PMID:26982086

  5. Individual Case Analysis of Postmortem Interval Time on Brain Tissue Preservation.

    PubMed

    Blair, Jeffrey A; Wang, Chunyu; Hernandez, Damarys; Siedlak, Sandra L; Rodgers, Mark S; Achar, Rojan K; Fahmy, Lara M; Torres, Sandy L; Petersen, Robert B; Zhu, Xiongwei; Casadesus, Gemma; Lee, Hyoung-Gon

    2016-01-01

    At autopsy, the time that has elapsed since the time of death is routinely documented and noted as the postmortem interval (PMI). The PMI of human tissue samples is a parameter often reported in research studies and comparable PMI is preferred when comparing different populations, i.e., disease versus control patients. In theory, a short PMI may alleviate non-experimental protein denaturation, enzyme activity, and other chemical changes such as the pH, which could affect protein and nucleic acid integrity. Previous studies have compared PMI en masse by looking at many different individual cases each with one unique PMI, which may be affected by individual variance. To overcome this obstacle, in this study human hippocampal segments from the same individuals were sampled at different time points after autopsy creating a series of PMIs for each case. Frozen and fixed tissue was then examined by Western blot, RT-PCR, and immunohistochemistry to evaluate the effect of extended PMI on proteins, nucleic acids, and tissue morphology. In our results, immunostaining profiles for most proteins remained unchanged even after PMI of over 50 h, yet by Western blot distinctive degradation patterns were observed in different protein species. Finally, RNA integrity was lower after extended PMI; however, RNA preservation was variable among cases suggesting antemortem factors may play a larger role than PMI in protein and nucleic acid integrity. PMID:26982086

  6. BDNF promoter I methylation correlates between post-mortem human peripheral and brain tissues.

    PubMed

    Stenz, Ludwig; Zewdie, Seblewongel; Laforge-Escarra, Térèse; Prados, Julien; La Harpe, Romano; Dayer, Alexandre; Paoloni-Giacobino, Ariane; Perroud, Nader; Aubry, Jean-Michel

    2015-02-01

    Several psychiatric disorders have been associated with CpG methylation changes in CG rich promoters of the brain-derived neurotrophic factor (BDNF) mainly by extracting DNA from peripheral blood cells. Whether changes in peripheral DNA methylation can be used as a proxy for brain-specific alterations remains an open question. In this study we aimed to compare DNA methylation levels in BDNF promoter regions in human blood cells, muscle and brain regions using bisulfite-pyrosequencing. We found a significant correlation between the levels of BDNF promoter I methylation measured in quadriceps and vPFC tissues extracted from the same individuals (n = 98, Pearson, r = 0.48, p = 4.5 × 10(-7)). In the hippocampus, BDNF promoter I and IV methylation levels were strongly correlated (Pearson, n = 37, r = 0.74, p = 1.4 × 10(-7)). We found evidence for sex-dependent effect on BDNF promoter methylation levels in the various tissues and blood samples. Taken together, these data indicate a strong intra-individual correlation between peripheral and brain tissue. They also suggest that sex determines methylation patterns in BDNF promoter region across different types of tissue, including muscle, brain, and blood. PMID:25450314

  7. Metabolic signatures of Huntington's disease (HD): (1)H NMR analysis of the polar metabolome in post-mortem human brain.

    PubMed

    Graham, Stewart F; Kumar, Praveen K; Bjorndahl, Trent; Han, BeomSoo; Yilmaz, Ali; Sherman, Eric; Bahado-Singh, Ray O; Wishart, David; Mann, David; Green, Brian D

    2016-09-01

    Huntington's disease (HD) is an autosomal neurodegenerative disorder affecting approximately 5-10 persons per 100,000 worldwide. The pathophysiology of HD is not fully understood but the age of onset is known to be highly dependent on the number of CAG triplet repeats in the huntingtin gene. Using (1)H NMR spectroscopy this study biochemically profiled 39 brain metabolites in post-mortem striatum (n=14) and frontal lobe (n=14) from HD sufferers and controls (n=28). Striatum metabolites were more perturbed with 15 significantly affected in HD cases, compared with only 4 in frontal lobe (p<0.05; q<0.3). The metabolite which changed most overall was urea which decreased 3.25-fold in striatum (p<0.01). Four metabolites were consistently affected in both brain regions. These included the neurotransmitter precursors tyrosine and l-phenylalanine which were significantly depleted by 1.55-1.58-fold and 1.48-1.54-fold in striatum and frontal lobe, respectively (p=0.02-0.03). They also included l-leucine which was reduced 1.54-1.69-fold (p=0.04-0.09) and myo-inositol which was increased 1.26-1.37-fold (p<0.01). Logistic regression analyses performed with MetaboAnalyst demonstrated that data obtained from striatum produced models which were profoundly more sensitive and specific than those produced from frontal lobe. The brain metabolite changes uncovered in this first (1)H NMR investigation of human HD offer new insights into the disease pathophysiology. Further investigations of striatal metabolite disturbances are clearly warranted. PMID:27288730

  8. In Situ Biospectroscopic Investigation of Rapid Ischemic and Postmortem Induced Biochemical Alterations in the Rat Brain

    PubMed Central

    2015-01-01

    Rapid advances in imaging technologies have pushed novel spectroscopic modalities such as Fourier transform infrared spectroscopy (FTIR) and X-ray absorption spectroscopy (XAS) at the sulfur K-edge to the forefront of direct in situ investigation of brain biochemistry. However, few studies have examined the extent to which sample preparation artifacts confound results. Previous investigations using traditional analyses, such as tissue dissection, homogenization, and biochemical assay, conducted extensive research to identify biochemical alterations that occur ex vivo during sample preparation. In particular, altered metabolism and oxidative stress may be caused by animal death. These processes were a concern for studies using biochemical assays, and protocols were developed to minimize their occurrence. In this investigation, a similar approach was taken to identify the biochemical alterations that are detectable by two in situ spectroscopic methods (FTIR, XAS) that occur as a consequence of ischemic conditions created during humane animal killing. FTIR and XAS are well suited to study markers of altered metabolism such as lactate and creatine (FTIR) and markers of oxidative stress such as aggregated proteins (FTIR) and altered thiol redox (XAS). The results are in accordance with previous investigations using biochemical assays and demonstrate that the time between animal death and tissue dissection results in ischemic conditions that alter brain metabolism and initiate oxidative stress. Therefore, future in situ biospectroscopic investigations utilizing FTIR and XAS must take into consideration that brain tissue dissected from a healthy animal does not truly reflect the in vivo condition, but rather reflects a state of mild ischemia. If studies require the levels of metabolites (lactate, creatine) and markers of oxidative stress (thiol redox) to be preserved as close as possible to the in vivo condition, then rapid freezing of brain tissue via decapitation into

  9. Enzymes in the glutamate-glutamine cycle in the anterior cingulate cortex in postmortem brain of subjects with autism

    PubMed Central

    2013-01-01

    Background Accumulating evidence suggests that dysfunction in the glutamatergic system may underlie the pathophysiology of autism. The anterior cingulate cortex (ACC) has been implicated in autism as well as in glutamatergic neurotransmission. We hypothesized that alterations in the glutamate-glutamine cycle in the ACC might play a role in the pathophysiology of autism. Methods We performed Western blot analyses for the protein expression levels of enzymes in the glutamate-glutamine cycle, including glutamine synthetase, kidney-type glutaminase, liver-type glutaminase, and glutamate dehydrogenases 1 and 2, in the ACC of postmortem brain of individuals with autism (n = 7) and control subjects (n = 13). Results We found that the protein levels of kidney-type glutaminase, but not those of the other enzymes measured, in the ACC were significantly lower in subjects with autism than in controls. Conclusion The results suggest that reduced expression of kidney-type glutaminase may account for putative alterations in glutamatergic neurotransmission in the ACC in autism. PMID:23531457

  10. Regulation of complement factor H (CFH) by multiple miRNAs in Alzheimer's disease (AD) brain.

    PubMed

    Lukiw, Walter J; Alexandrov, Peter N

    2012-08-01

    Human brain cells rely on a specific subset of microRNAs (miRNAs or miRs) to shape their gene expression patterns, and this is mediated through microRNA effects on messenger RNA (mRNA) speciation and complexity. In recent studies (a) in short post-mortem interval Alzheimer's disease (AD) brain tissues versus age-matched controls, and (b) in pro-inflammatory cytokine- and Aβ42 peptide-stressed human neuronal-glial (HNG) cells in primary culture, we have identified several brain-abundant miRNA species found to be significantly up-regulated, including miR-125b and miR-146a. Both of these nuclear factor kappa B (NF-κB)-activated, 22 nucleotide small non-coding RNAs (sncRNAs) target the mRNA of the key, innate-immune- and inflammation-related regulatory protein, complement factor-H (CFH; chr 1q32), resulting in significant decreases in CFH expression (p < 0.01, ANOVA). Our results further indicate that HNG cells respond to IL-1β + Aβ42-peptide-induced stress by significant NF-κB-modulated up-regulation of miRNA-125b- and miRNA-146a. The complex interactive signaling of NF-κB, miR-125b, miR-146a, and perhaps other miRNAs, further illustrate interplay between inducible transcription factors and multiple pro-inflammatory sncRNAs that regulate CFH expression. The novel concept of miRNA actions involving mRNA target convergence and divergence are proposed and discussed. The combinatorial use of NF-кB inhibitors with anti-miRNAs (AMs; antagomirs) may have potential against CFH-driven pathogenic signaling in neurodegenerative disease, and may redirect our therapeutic perspectives to novel treatment strategies that have not yet been considered. PMID:22302353

  11. The norepinephrine transporter (NET) radioligand (S,S)-[18F]FMeNER-D2 shows significant decreases in NET density in the human brain in Alzheimer's disease: a post-mortem autoradiographic study.

    PubMed

    Gulyás, Balázs; Brockschnieder, Damian; Nag, Sangram; Pavlova, Elena; Kása, Péter; Beliczai, Zsuzsa; Légrádi, Adám; Gulya, Károly; Thiele, Andrea; Dyrks, Thomas; Halldin, Christer

    2010-01-01

    Earlier post-mortem histological and autoradiographic studies have indicated a reduction of cell numbers in the locus coeruleus (LC) and a corresponding decrease in norepinephrine transporter (NET) in brains obtained from Alzheimer's disease (AD) patients as compared to age-matched healthy controls. In order to test the hypothesis that the regional decrease of NET is a disease specific biomarker in AD and as such, it can be used in PET imaging studies for diagnostic considerations, regional differences in the density of NET in various anatomical structures were measured in whole hemisphere human brain slices obtained from AD patients and age-matched control subjects in a series of autoradiographic experiments using the novel selective PET radioligand for NET (S,S)-[(18)F]FMeNER-D(2). (S,S)-[(18)F]FMeNER-D(2) appears to be a useful imaging biomarker for quantifying the density of NET in various brain structures, including the LC and the thalamus wherein the highest densities are found in physiological conditions. In AD significant decreases of NET densities can be demonstrated with the radioligand in both structures as compared to age-matched controls. The decreases in AD correlate with the progress of the disease as indicated by Braak grades. As the size of the LC is below the spatial resolution of the PET scanners, but the size of the thalamus can be detected with appropriate spatial accuracy in advanced scanners, the present findings confirm our earlier observations with PET that the in vivo imaging of NET with (S,S)-[(18)F]FMeNER-D(2) in the thalamus is viable. Nevertheless, further studies are warranted to assess the usefulness of such an imaging approach for the early detection of changes in thalamic NET densities as a disease-specific biomarker and the possible use of (S,S)-[(18)F]FMeNER-D(2) as a molecular imaging biomarker in AD. PMID:20211213

  12. Stability and Autolysis of Cortical Neurons in Post-Mortem Adult Rat Brains

    PubMed Central

    Sheleg, Sergey V; LoBello, Janine R; Hixon, Hugh; Coons, Stephen W; Lowry, David; Nedzved, Mikhail K

    2008-01-01

    We investigated the dynamics of autolytic damage of the cortical neurons in adult brains for 24 hours at room temperature (+20°C) after cardiac arrest. The progressive histological and ultrastructural changes were documented using routine and immunohistochemical staining as well as electron microscopy. Our results demonstrated that there were no autolytic damages in the ultrastructure of cerebral neurons in the first 6 hours after warm cardiac arrest, in agreement with previous studies in other mammals. Interestingly, the activation of caspase-3 was observed in a significant number of neurons of the cerebellum and neocortex 9 hours following cardiac arrest. No significant changes related to autolysis were observed using amnio-cupric acid and Nissl (thionine) staining. PMID:18784829

  13. Postmortem aging and freezing and thawing storage enhance ability of early deboned chicken pectoralis major muscle to hold added salt water

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The effects of postdeboning aging and frozen storage on water-holding capacity (WHC) of chicken breast pectoralis major muscle were investigated. Broiler breast muscle was removed from carcasses either early postmortem (2 h) or later postmortem (24 h). Treatments included: no postdeboning aging; 1-...

  14. Development, appraisal, validation and implementation of a consensus protocol for the assessment of cerebral amyloid angiopathy in post-mortem brain tissue

    PubMed Central

    Love, Seth; Chalmers, Katy; Ince, Paul; Esiri, Margaret; Attems, Johannes; Kalaria, Raj; Jellinger, Kurt; Yamada, Masahito; McCarron, Mark; Minett, Thais; Matthews, Fiona; Greenberg, Steven; Mann, David; Kehoe, Patrick Gavin

    2015-01-01

    In a collaboration involving 11 groups with research interests in cerebral amyloid angiopathy (CAA), we used a two-stage process to develop and in turn validate a new consensus protocol and scoring scheme for the assessment of CAA and associated vasculopathic abnormalities in post-mortem brain tissue. Stage one used an iterative Delphi-style survey to develop the consensus protocol. The resultant scoring scheme was tested on a series of digital images and paraffin sections that were circulated blind to a number of scorers. The scoring scheme and choice of staining methods were refined by open-forum discussion. The agreed protocol scored parenchymal and meningeal CAA on a 0-3 scale, capillary CAA as present/absent and vasculopathy on 0-2 scale, in the 4 cortical lobes that were scored separately. A further assessment involving three centres was then undertaken. Neuropathologists in three centres (Bristol, Oxford and Sheffield) independently scored sections from 75 cases (25 from each centre) and high inter-rater reliability was demonstrated. Stage two used the results of the three-centre assessment to validate the protocol by investigating previously described associations between APOE genotype (previously determined), and both CAA and vasculopathy. Association of capillary CAA with or without arteriolar CAA with APOE ε4 was confirmed. However APOE ε2 was also found to be a strong risk factor for the development of CAA, not only in AD but also in elderly non-demented controls. Further validation of this protocol and scoring scheme is encouraged, to aid its wider adoption to facilitate collaborative and replication studies of CAA. PMID:26807344

  15. Optical properties of rabbit brain in the red and near-infrared: changes observed under in vivo, postmortem, frozen, and formalin-fixated conditions

    NASA Astrophysics Data System (ADS)

    Pitzschke, Andreas; Lovisa, Blaise; Seydoux, Olivier; Haenggi, Matthias; Oertel, Markus F.; Zellweger, Matthieu; Tardy, Yanik; Wagnières, Georges

    2015-02-01

    The outcome of light-based therapeutic approaches depends on light propagation in biological tissues, which is governed by their optical properties. The objective of this study was to quantify optical properties of brain tissue in vivo and postmortem and assess changes due to tissue handling postmortem. The study was carried out on eight female New Zealand white rabbits. The local fluence rate was measured in the VIS/NIR range in the brain in vivo, just postmortem, and after six weeks' storage of the head at -20°C or in 10% formaldehyde solution. Only minimal changes in the effective attenuation coefficient μeff were observed for two methods of sacrifice, exsanguination or injection of KCl. Under all tissue conditions, μeff decreased with increasing wavelengths. After long-term storage for six weeks at -20°C, μeff decreased, on average, by 15 to 25% at all wavelengths, while it increased by 5 to 15% at all wavelengths after storage in formaldehyde. We demonstrated that μeff was not very sensitive to the method of animal sacrifice, that tissue freezing significantly altered tissue optical properties, and that formalin fixation might affect the tissue's optical properties.

  16. Post-mortem brain pathology is related to declining respiratory function in community-dwelling older adults

    PubMed Central

    Buchman, Aron S.; Yu, Lei; Wilson, Robert S.; Dawe, Robert J.; VanderHorst, Veronique; Schneider, Julie A.; Bennett, David A.

    2015-01-01

    Damage to brain structures which constitute the distributed neural network that integrates respiratory muscle and pulmonary functions, can impair adequate ventilation and its volitional control. We tested the hypothesis that the level of brain pathology in older adults is associated with declining respiratory function measured during life. 1,409 older adults had annual testing with spirometry (SPI) and respiratory muscle strength (RMS) based on maximal inspiratory and maximal expiratory pressures (MEPs). Those who died underwent structured brain autopsy. On average, during 5 years of follow-up, SPI and RMS showed progressive decline which was moderately correlated (ρ = 0.57, p < 0.001). Among decedents (N = 447), indices of brain neuropathologies showed differential associations with declining SPI and RMS. Nigral neuronal loss was associated with the person-specific decline in SPI (Estimate, −0.016 unit/year, S.E. 0.006, p = 0.009) and reduction of the slope variance was equal to 4%. By contrast, Alzheimer’s disease (AD) pathology (Estimate, −0.030 unit/year, S.E. 0.009, p < 0.001) and macroscopic infarcts (−0.033 unit/year, S.E., 0.011, p = 0.003) were associated with the person-specific decline in RMS and reduction of the slope variance was equal to 7%. These results suggest that brain pathology is associated with the rate of declining respiratory function in older adults. PMID:26539108

  17. Identification of N-terminally truncated pyroglutamate amyloid-β in cholesterol-enriched diet-fed rabbit and AD brain.

    PubMed

    Perez-Garmendia, Roxanna; Hernandez-Zimbron, Luis Fernando; Morales, Miguel Angel; Luna-Muñoz, José; Mena, Raul; Nava-Catorce, Miriam; Acero, Gonzalo; Vasilevko, Vitaly; Viramontes-Pintos, Amparo; Cribbs, David H; Gevorkian, Goar

    2014-01-01

    The main amyloid-β peptide (Aβ) variants detected in the human brain are Aβ1-40 and Aβ1-42; however, a significant proportion of Aβ in Alzheimer's disease (AD) brain also consists of N-terminal truncated/modified species. AβN3(pE), Aβ peptide bearing amino-terminal pyroglutamate at position 3, has been demonstrated to be a major N-truncated/modified constituent of intracellular, extracellular, and vascular Aβ deposits in AD and Down syndrome brain tissue. It has been previously demonstrated that rabbits fed a diet enriched in cholesterol and given water containing trace copper levels developed AD-like pathology including intraneuronal and extracellular Aβ accumulation, tau hyperphosphorylation, vascular inflammation, astrocytosis, microgliosis, reduced levels of acetylcholine, as well as learning deficits and thus, may be used as a non-transgenic animal model of sporadic AD. In the present study, we have demonstrated for the first time the presence of AβN3(pE) in blood vessels in cholesterol-enriched diet-fed rabbit brain. In addition, we detected AβN3(pE) immunoreactivity in all postmortem AD brain samples studied. We believe that our results are potentially important for evaluation of novel therapeutic molecules/strategies targeting Aβ peptides in a suitable non-transgenic animal model. PMID:24240639

  18. Antipsychotic drugs attenuate aberrant DNA methylation of DTNBP1 (dysbindin) promoter in saliva and post-mortem brain of patients with schizophrenia and Psychotic bipolar disorder.

    PubMed

    Abdolmaleky, Hamid M; Pajouhanfar, Sara; Faghankhani, Masoomeh; Joghataei, Mohammad Taghi; Mostafavi, Ashraf; Thiagalingam, Sam

    2015-12-01

    Due to the lack of genetic association between individual genes and schizophrenia (SCZ) pathogenesis, the current consensus is to consider both genetic and epigenetic alterations. Here, we report the examination of DNA methylation status of DTNBP1 promoter region, one of the most credible candidate genes affected in SCZ, assayed in saliva and post-mortem brain samples. The Illumina DNA methylation profiling and bisulfite sequencing of representative samples were used to identify methylation status of the DTNBP1 promoter region. Quantitative methylation specific PCR (qMSP) was employed to assess methylation of DTNBP1 promoter CpGs flanking a SP1 binding site in the saliva of SCZ patients, their first-degree relatives and control subjects (30, 15, and 30/group, respectively) as well as in post-mortem brains of patients with SCZ and bipolar disorder (BD) versus controls (35/group). qRT-PCR was used to assess DTNBP1 expression. We found DNA hypermethylation of DTNBP1 promoter in the saliva of SCZ patients (∼12.5%, P = 0.036), particularly in drug-naïve patients (∼20%, P = 0.011), and a trend toward hypermethylation in their first-degree relatives (P = 0.085) versus controls. Analysis of post-mortem brain samples revealed an inverse correlation between DTNBP1 methylation and expression, and normalization of this epigenetic change by classic antipsychotic drugs. Additionally, BD patients with psychotic depression exhibited higher degree of methylation versus other BD patients (∼80%, P = 0.025). DTNBP1 promoter DNA methylation may become a key element in a panel of biomarkers for diagnosis, prevention, or therapy in SCZ and at risk individuals pending confirmatory studies with larger sample sizes to attain a higher degree of significance. PMID:26285059

  19. Candidate PET Radioligand Development for Neurofibrillary Tangles: Two Distinct Radioligand Binding Sites Identified in Postmortem Alzheimer's Disease Brain.

    PubMed

    Cai, Lisheng; Qu, Baoxi; Hurtle, Bryan T; Dadiboyena, Sureshbabu; Diaz-Arrastia, Ramon; Pike, Victor W

    2016-07-20

    [(18)F]THK-523 and [(18)F]807 are promising radioligands for imaging neurofibrillary tangles (NFTs) with positron emission tomography (PET) in neurodegenerative diseases, such as Alzheimer's disease (AD) and traumatic brain injury. Although [(18)F]THK-523 and [(18)F]T807 are considered high-affinity selective radioligands for NFTs, uncertainty has existed as to whether PET radioligands for imaging NFTs bind to the same molecular site because in vitro assays for ligands binding to NFTs have been lacking. We labeled THK-523 and T807 with tritium to serve as reference radioligands for in vitro binding assays with AD brain homogenates for newly synthesized ligands. With these radioligands, we identified two distinct binding sites for small molecules, one site with high affinity for THK-523 and the other with high affinity for T807. Moreover, binding assays with [(3)H]PIB confirmed that the two newly identified binding sites are also distinct from the thioflavin-T binding site where all current clinically useful PET radioligands for imaging β-amyloid plaque bind with high affinity. The two newly identified binding sites are considered to reside on NFTs rather than on β-amyloid plaques. Furthermore, we applied all three binding assays to a set of newly prepared compounds, based on chain modifications to THK-523. Some compounds with high affinity and selectivity for the THK-523 binding site emerged from this set, including one with amenability to labeling with fluorine-18, namely, ligand 10b. PMID:27171905

  20. Effects of postmortem delays on protein composition and oxidation.

    PubMed

    ElHajj, Zeinab; Cachot, Amélie; Müller, Terry; Riederer, Irène M; Riederer, Beat M

    2016-03-01

    Human autopsy brain tissue is widely used to study neurodegenerative diseases such as Alzheimer's, Parkinson's and other diseases. However, when it comes to an evaluation of data obtained from such tissue, it is essential to consider potential postmortem effects on protein composition, posttranslational modification and proteolysis with increasing postmortem delays. In this study, we analyzed mouse brain tissues with different postmortem delays (pmd) of 0 h, 6h and 24h, for changes in protein composition, proteolysis and modifications such as S-nitrosylation, carbonylation and ubiquitination. Proteins involved in Alzheimer's disease (AD) were of special interest, including cytoskeletal and synaptic proteins or proteins involved in inflammation. Several proteins were fairly resistant to degradation during the first 6h but started to degrade thereafter. S-nitrosylation and carbonylation showed not much variation, except for those proteins that were susceptible to degradation. Brain spectrin was S-nitrosylated at death, and S-nitrosylated degradation fragments were measured at a pmd of 24h, indicating a susceptibility of brain spectrin to degradation. Furthermore, the physiological role of S-nitrosylation remains to be investigated. When studying human brain tissue, some proteins are more susceptible to degradation than others, while ubiquitination and carbonylation were little affected during the first 24h after death. PMID:26791740

  1. Postmortem imaging: MDCT features of postmortem change and decomposition.

    PubMed

    Levy, Angela D; Harcke, Howard Theodore; Mallak, Craig T

    2010-03-01

    Multidetector computed tomography (MDCT) has emerged as an effective imaging technique to augment forensic autopsy. Postmortem change and decomposition are always present at autopsy and on postmortem MDCT because they begin to occur immediately upon death. Consequently, postmortem change and decomposition on postmortem MDCT should be recognized and not mistaken for a pathologic process or injury. Livor mortis increases the attenuation of vasculature and dependent tissues on MDCT. It may also produce a hematocrit effect with fluid levels in the large caliber blood vessels and cardiac chambers from dependent layering erythrocytes. Rigor mortis and algor mortis have no specific MDCT features. In contrast, decomposition through autolysis, putrefaction, and insect and animal predation produce dramatic alterations in the appearance of the body on MDCT. Autolysis alters the attenuation of organs. The most dramatic autolytic changes on MDCT are seen in the brain where cerebral sulci and ventricles are effaced and gray-white matter differentiation is lost almost immediately after death. Putrefaction produces a pattern of gas that begins with intravascular gas and proceeds to gaseous distension of all anatomic spaces, organs, and soft tissues. Knowledge of the spectrum of postmortem change and decomposition is an important component of postmortem MDCT interpretation. PMID:20010292

  2. Chiral analysis of methadone and its main metabolite, EDDP, in postmortem brain and blood by automated SPE and liquid chromatography-mass spectrometry.

    PubMed

    Holm, Karen Marie Dollerup; Linnet, Kristian

    2012-09-01

    We developed a method based on liquid chromatography coupled with tandem mass spectrometry to quantify individual enantiomers of methadone and its primary metabolite, R/S-2-ethyl-1,5-dimethyl-3,3-diphenylpyrrolinium (EDDP), in postmortem blood and brain tissue. Samples were prepared with a Tecan Evo robotic system. Precipitation was followed by solid-phase extraction, evaporation and reconstitution in the mobile phase. Enantiomers were fully separated with liquid chromatography on a chiral α(1)-acid glycoprotein column. A Quattro micro mass spectrometer was used for detection in the positive ion mode with an electrospray source. The lower limit of quantification in brain tissue was 0.005 mg/kg for methadone and 0.001 mg/kg for EDDP enantiomers; the maximum precision was 17% for both compounds; accuracy ranged from 94 to 101%. In blood, the limit of quantification was 0.001 mg/kg for all compounds, the total relative standard deviation was <15%, and the accuracy varied from 95 to 109%. Brain (n = 11) and blood (n = 15) samples were analyzed with intermediate precision that varied from 7.5 to 15% at 0.005 mg/kg and from 6.8 to 11.3% at 0.25 mg/kg for all compounds. Method development focused on producing a clean extract, particularly from brain samples. The method was tested on authentic brain and femoral blood samples. PMID:22778199

  3. Expression of CHRFAM7A and CHRNA7 in neuronal cells and postmortem brain of HIV-infected patients: considerations for HIV-associated neurocognitive disorder.

    PubMed

    Ramos, Félix M; Delgado-Vélez, Manuel; Ortiz, Ángel L; Báez-Pagán, Carlos A; Quesada, Orestes; Lasalde-Dominicci, José A

    2016-06-01

    Despite the recent advances in antiretroviral therapy, human immunodeficiency virus type 1 (HIV-1) remains a global health threat. HIV-1 affects the central nervous system by releasing viral proteins that trigger neuronal death and neuroinflammation, and promotes alterations known as HIV-associated neurocognitive disorders (HAND). This disorder is not fully understood, and no specific treatments are available. Recently, we demonstrated that the HIV-1 envelope protein gp120IIIB induces a functional upregulation of the α7-nicotinic acetylcholine receptor (α7) in neuronal cells. Furthermore, this upregulation promotes cell death that can be abrogated with receptor antagonists, suggesting that α7 may play an important role in the development of HAND. The partial duplication of the gene coding for the α7, known as CHRFAM7A, negatively regulates α7 expression but its role in HIV infection has not been studied. Hence, we studied both CHRNA7 and CHRFAM7A regulation patterns in various gp120IIIB in vitro conditions. In addition, we measured CHRNA7 and CHRFAM7A expression levels in postmortem brain samples from patients suffering from different stages of HAND. Our results demonstrate the induction of CHRNA7 expression accompanied by a significant downregulation of CHRFAM7A in neuronal cells when exposed to pathophysiological concentrations of gp120IIIB. Our results suggest a dysregulation of CHRFAM7A and CHRNA7 expressions in the basal ganglia from postmortem brain samples of HIV+ subjects and expand the current knowledge about the consequences of HIV infection in the brain. PMID:26567012

  4. Differential Impact of Whole-Brain Radiotherapy Added to Radiosurgery for Brain Metastases

    SciTech Connect

    Kong, Doo-Sik; Lee, Jung-Il; Im, Yong-Seok; Nam, Do-Hyun; Park, Kwan; Kim, Jong-Hyun

    2010-10-01

    Purpose: The authors investigated whether the addition of whole-brain radiotherapy (WBRT) to stereotactic radiosurgery (SRS) provided any therapeutic benefit according to recursive partitioning analysis (RPA) class. Methods and Materials: Two hundred forty-five patients with 1 to 10 metastases who underwent SRS between January 2002 and December 2007 were included in the study. Of those, 168 patients were treated with SRS alone and 77 patients received SRS followed by WBRT. Actuarial curves were estimated using the Kaplan-Meier method regarding overall survival (OS), distant brain control (DC), and local brain control (LC) stratified by RPA class. Analyses for known prognostic variables were performed using the Cox proportional hazards model. Results: Univariate and multivariate analysis revealed that control of the primary tumor, small number of brain metastases, Karnofsky performance scale (KPS) > 70, and initial treatment modalities were significant predictors for survival. For RPA class 1, SRS plus WBRT was associated with a longer survival time compared with SRS alone (854 days vs. 426 days, p = 0.042). The SRS plus WBRT group also showed better LC rate than did the SRS-alone group (p = 0.021), although they did not show a better DC rate (p = 0.079). By contrast, for RPA class 2 or 3, no significant difference in OS, LC, or DC was found between the two groups. Conclusions: These results suggest that RPA classification should determine whether or not WBRT is added to SRS. WBRT may be recommended to be added to SRS for patients in whom long-term survival is expected on the basis of RPA classification.

  5. Optical properties of the deep brain in the red and NIR: changes observed under in-vivo, post-mortem, frozen and formalin-fixated conditions

    NASA Astrophysics Data System (ADS)

    Pitzschke, A.; Lovisa, B.; Seydoux, O.; Zellweger, M.; Pfleiderer, M.; Haenggi, M.; Oertel, M.; Tardy, Y.; Wagnières, G.

    2015-07-01

    Photobiomodulation (PBM) is a promising approach to treat Parkinson's disease (PD) symptoms in cellular or animal models. Unfortunately, little information is available on the optical parameters playing a role in the light dosimetry during PBM. We conducted a study to determine the effective attenuation coefficient μeff of PD-relevant human deep brain tissues at 671 and 808 nm, using a multichannel fluence rate-meter comprising sub-millimeter isotropic detectors. The first step involved measurements of tissue modifications induced by postmortem situation and tissue storage on rabbit brains. The parameter μeff was measured using various tissue conditions (in vivo, immediately after sacrifice, after six weeks' storage at -20°C or in 10 % formaldehyde solution) on eight female New Zealand white rabbits. In the second step, fluence rate was measured at various locations of a frozen human deep brain when the deep brain was illuminated from the sphenoidal sinus. The results were processed by an iterative Monte-Carlo algorithm to generate sets of optical parameters, and results collected on rabbit brains were used to extrapolate the μeff value that would be observed in human deep brain tissues in vivo. Under all tissue conditions, the value of μeff at 808 nm was smaller than that at 671 nm. After long-term storage for six weeks at -20°C, μeff decreased, on average by 15 to 25 % at all wavelengths, while it increased by 5 to 15 % at all wavelengths after storage in formaldehyde. Therefore, a reasonable estimate of in vivo human deep brain μeff values at 671 and 808 nm can be obtained by multiplying the data we report by 120 %.

  6. Cyclic AMP response element-binding protein in post-mortem brain of teenage suicide victims: specific decrease in the prefrontal cortex but not the hippocampus.

    PubMed

    Pandey, Ghanshyam N; Dwivedi, Yogesh; Ren, Xinguo; Rizavi, Hooriyah S; Roberts, Rosalinda C; Conley, Robert R

    2007-10-01

    Abnormalities in both adenylyl cyclase (AC) and phosphoinositide (PI) signalling systems have been observed in the post-mortem brain of suicide victims. Cyclic AMP response element-binding protein (CREB) is a transcription factor that is activated by phosphorylating enzymes such as protein kinase A (PKA) and protein kinase C (PKC), which suggests that both AC and PI signalling systems converge at the level of CREB. CREB is involved in the transcription of many neuronally expressed genes that have been implicated in the pathophysiology of depression and suicide. Since we observed abnormalities of both PKA and PKC in the post-mortem brain of teenage suicide victims, we examined if these abnormalities are also associated with abnormalities of CREB, which is activated by these phosphorylating enzymes. We determined CRE-DNA binding using the gel shift assay, as well as protein expression of CREB using the Western blot technique, and the mRNA expression of CREB using a quantitative reverse transcriptase-polymerase chain reaction (RT-PCR) technique in the prefrontal cortex (PFC), and hippocampus obtained from 17 teenage suicide victims and 17 matched normal control subjects. We observed that the CRE-DNA binding and the protein expression of CREB were significantly decreased in the PFC of teenage suicide victims compared with controls. There was also a significant decrease in mRNA expression of CREB in the PFC of teenage suicide victims compared with control subjects. However, there were no significant differences in CRE-DNA binding or the protein and mRNA expression of CREB in the hippocampus of teenage suicide victims compared with control subjects. These results suggest that the abnormalities of PKA, and of PKC, observed in teenage suicide victims are also associated with abnormalities of the transcription factor CREB, and that this may also cause alterations of important neuronally expressed genes, and provide further support of the signal transduction of abnormalities

  7. Revisiting DARPP-32 in postmortem human brain: changes in schizophrenia and bipolar disorder and genetic associations with t-DARPP-32 expression.

    PubMed

    Kunii, Y; Hyde, T M; Ye, T; Li, C; Kolachana, B; Dickinson, D; Weinberger, D R; Kleinman, J E; Lipska, B K

    2014-02-01

    Dopamine- and cAMP-regulated phosphoprotein of molecular weight 32 kDa (DARPP-32 or PPP1R1B) has been of interest in schizophrenia owing to its critical function in integrating dopaminergic and glutaminergic signaling. In a previous study, we identified single-nucleotide polymorphisms (SNPs) and a frequent haplotype associated with cognitive and imaging phenotypes that have been linked with schizophrenia, as well as with expression of prefrontal cortical DARPP-32 messenger RNA (mRNA) in a relatively small sample of postmortem brains. In this study, we examined the association of expression of two major DARPP-32 transcripts, full-length (FL-DARPP-32) and truncated (t-DARPP-32), with genetic variants of DARPP-32 in three brain regions receiving dopaminergic input and implicated in schizophrenia (the dorsolateral prefrontal cortex (DLPFC), hippocampus and caudate) in a much larger set of postmortem samples from patients with schizophrenia, bipolar disorder, major depression and normal controls (>700 subjects). We found that the expression of t-DARPP-32 was increased in the DLPFC of patients with schizophrenia and bipolar disorder, and was strongly associated with genotypes at SNPs (rs879606, rs90974 and rs3764352), as well as the previously identified 7-SNP haplotype related to cognitive functioning. The genetic variants that predicted worse cognitive performance were associated with higher t-DARPP-32 expression. Our results suggest that variation in PPP1R1B affects the abundance of the splice variant t-DARPP-32 mRNA and may reflect potential molecular mechanisms implicated in schizophrenia and affective disorders. PMID:23295814

  8. Network Topology Analysis of Post-Mortem Brain Microarrays Identifies More Alzheimer’s Related Genes and MicroRNAs and Points to Novel Routes for Fighting with the Disease

    PubMed Central

    Chandrasekaran, Sreedevi; Bonchev, Danail

    2016-01-01

    Network-based approaches are powerful and beneficial tools to study complex systems in their entirety, elucidating the essential factors that turn the multitude of individual elements into a functional system. In this study we used critical network topology descriptors and guilt-by-association rule to explore and understand the significant molecular players, drug targets and underlying biological mechanisms of Alzheimer’s disease. Analyzing two post-mortem brain gene microarrays (GSE4757 and GSE28146) with Pathway Studio software package we constructed and analyzed a set of protein-protein interaction, as well as miRNA-target networks. In a 4-step procedure the expression datasets were normalized using Robust Multi-array Average approach, while the modulation of gene expression by the disease was statistically evaluated by the empirical Bayes method from the limma Bioconductor package. Representative set of 214 seed-genes (p<0.01) common for the three brain sections of the two microarrays was thus created. The Pathway Studio analysis of the networks built identified 15 new potential AD-related genes and 17 novel AD-involved microRNAs. Using KEGG pathways relevant in Alzheimer’s disease we built an integrated mechanistic network from the interactions between the overlapping genes in these pathways. Routes of possible disease initiation process were thus revealed through the CD4, DCN, and IL8 extracellular ligands. DAVID and IPA enrichment analysis uncovered a number of deregulated biological processes and pathways including neuron projection/differentiation, aging, oxidative stress, chemokine/ neurotrophin signaling, long-term potentiation and others. The findings in this study offer information of interest for subsequent experimental studies. PMID:26784894

  9. Metabolomic Profiling of Post-Mortem Brain Reveals Changes in Amino Acid and Glucose Metabolism in Mental Illness Compared with Controls.

    PubMed

    Zhang, Rong; Zhang, Tong; Ali, Ali Muhsen; Al Washih, Mohammed; Pickard, Benjamin; Watson, David G

    2016-01-01

    Metabolomic profiling was carried out on 53 post-mortem brain samples from subjects diagnosed with schizophrenia, depression, bipolar disorder (SDB), diabetes, and controls. Chromatography on a ZICpHILIC column was used with detection by Orbitrap mass spectrometry. Data extraction was carried out with m/z Mine 2.14 with metabolite searching against an in-house database. There was no clear discrimination between the controls and the SDB samples on the basis of a principal components analysis (PCA) model of 755 identified or putatively identified metabolites. Orthogonal partial least square discriminant analysis (OPLSDA) produced clear separation between 17 of the controls and 19 of the SDB samples (R2CUM 0.976, Q2 0.671, p-value of the cross-validated ANOVA score 0.0024). The most important metabolites producing discrimination were the lipophilic amino acids leucine/isoleucine, proline, methionine, phenylalanine, and tyrosine; the neurotransmitters GABA and NAAG and sugar metabolites sorbitol, gluconic acid, xylitol, ribitol, arabinotol, and erythritol. Eight samples from diabetic brains were analysed, six of which grouped with the SDB samples without compromising the model (R2 CUM 0.850, Q2 CUM 0.534, p-value for cross-validated ANOVA score 0.00087). There appears on the basis of this small sample set to be some commonality between metabolic perturbations resulting from diabetes and from SDB. PMID:27076878

  10. Metabolomic Profiling of Post-Mortem Brain Reveals Changes in Amino Acid and Glucose Metabolism in Mental Illness Compared with Controls

    PubMed Central

    Zhang, Rong; Zhang, Tong; Ali, Ali Muhsen; Al Washih, Mohammed; Pickard, Benjamin; Watson, David G.

    2016-01-01

    Metabolomic profiling was carried out on 53 post-mortem brain samples from subjects diagnosed with schizophrenia, depression, bipolar disorder (SDB), diabetes, and controls. Chromatography on a ZICpHILIC column was used with detection by Orbitrap mass spectrometry. Data extraction was carried out with m/z Mine 2.14 with metabolite searching against an in-house database. There was no clear discrimination between the controls and the SDB samples on the basis of a principal components analysis (PCA) model of 755 identified or putatively identified metabolites. Orthogonal partial least square discriminant analysis (OPLSDA) produced clear separation between 17 of the controls and 19 of the SDB samples (R2CUM 0.976, Q2 0.671, p-value of the cross-validated ANOVA score 0.0024). The most important metabolites producing discrimination were the lipophilic amino acids leucine/isoleucine, proline, methionine, phenylalanine, and tyrosine; the neurotransmitters GABA and NAAG and sugar metabolites sorbitol, gluconic acid, xylitol, ribitol, arabinotol, and erythritol. Eight samples from diabetic brains were analysed, six of which grouped with the SDB samples without compromising the model (R2 CUM 0.850, Q2 CUM 0.534, p-value for cross-validated ANOVA score 0.00087). There appears on the basis of this small sample set to be some commonality between metabolic perturbations resulting from diabetes and from SDB. PMID:27076878

  11. Differential regional N-acetylaspartate deficits in postmortem brain in schizophrenia, bipolar disorder and major depressive disorder.

    PubMed

    Reynolds, Lindsay M; Reynolds, Gavin P

    2011-01-01

    There is substantial evidence for the involvement of the hippocampus and subcortical regions in the neuropathology of schizophrenia. Deficits of N-acetylaspartate (NAA) have been found in schizophrenia and bipolar disorder which may reflect neuronal loss and/or dysfunction. N-acetylaspartylglutamate (NAAG) is the most abundant peptide transmitter in the mammalian nervous system. It is an agonist at presynaptic metabotropic glutamate receptors mGluR3, inhibiting glutamate release. NAA and NAAG and were measured in hippocampal, striatal, amygdala and cingulate gyrus regions of human postmortem tissue from controls and subjects with schizophrenia, bipolar disorder and major depressive disorder. There are significant deficits in hippocampal NAA concentrations in all patient groups. In the amygdala there are significant NAA deficits in schizophrenia and depression and significant deficits of NAAG in the amygdala in the depression group. The deficits in NAA reported in this study confirm the importance of hippocampal and other subcortical structures in the neuropathology of the major psychiatric disorders. PMID:20684832

  12. Post-mortem Findings in Huntington’s Deep Brain Stimulation: A Moving Target Due to Atrophy

    PubMed Central

    Vedam-Mai, Vinata; Martinez-Ramirez, Daniel; Hilliard, Justin D.; Carbunaru, Samuel; Yachnis, Anthony T.; Bloom, Joshua; Keeling, Peyton; Awe, Lisa; Foote, Kelly D.; Okun, Michael S.

    2016-01-01

    Background Deep brain stimulation (DBS) has been shown to be effective for Parkinson’s disease, essential tremor, and primary dystonia. However, mixed results have been reported in Huntington’s disease (HD). Case Report A single case of HD DBS was identified from the University of Florida DBS Brain Tissue Network. The clinical presentation, evolution, surgical planning, DBS parameters, clinical outcomes, and brain pathological changes are summarized. Discussion This case of HD DBS revealed that chorea may improve and be sustained. Minimal histopathological changes were noted around the DBS leads. Severe atrophy due to HD likely changed the DBS lead position relative to the internal capsule. PMID:27127722

  13. Neurofibrillary tangle pathology and Braak staging in chronic epilepsy in relation to traumatic brain injury and hippocampal sclerosis: a post-mortem study

    PubMed Central

    Liu, Joan Y.W.; Thompson, Pam; Phadke, Rahul; Narkiewicz, Marta; Martinian, Lillian; Marsdon, Derek; Koepp, Matthias; Caboclo, Luis; Catarino, Claudia B.; Sisodiya, Sanjay M.

    2011-01-01

    The long-term pathological effects of chronic epilepsy on normal brain ageing are unknown. Previous clinical and epidemiological studies show progressive cognitive decline in subsets of patients and an increased prevalence of Alzheimer's disease in epilepsy. In a post-mortem series of 138 patients with long-term, mainly drug-resistant epilepsy, we carried out Braak staging for Alzheimer's disease neurofibrillary pathology using tau protein immunohistochemistry. The stages were compared with clinicopathological factors, including seizure history and presence of old traumatic brain injury. Overall, 31% of cases were Braak Stage 0, 36% Stage I/II, 31% Stage III/IV and 2% Stage V/VI. The mean age at death was 56.5 years and correlated with Braak stage (P < 0.001). Analysis of Braak stages within age groups showed a significant increase in mid-Braak stages (III/IV), in middle age (40–65 years) compared with data from an ageing non-epilepsy series (P < 0.01). There was no clear relationship between seizure type (generalized or complex partial), seizure frequency, age of onset and duration of epilepsy with Braak stage although higher Braak stages were noted with focal more than with generalized epilepsy syndromes (P < 0.01). In 30% of patients, there was pathological evidence of traumatic brain injury that was significantly associated with higher Braak stages (P < 0.001). Cerebrovascular disease present in 40.3% and cortical malformations in 11.3% were not significantly associated with Braak stage. Astrocytic-tau protein correlated with the presence of both traumatic brain injury (P < 0.01) and high Braak stage (P < 0.001). Hippocampal sclerosis, identified in 40% (bilateral in 48%), was not associated with higher Braak stages, but asymmetrical patterns of tau protein accumulation within the sclerotic hippocampus were noted. In over half of patients with cognitive decline, the Braak stage was low indicating causes other than Alzheimer's disease

  14. The Fluorescent Congo Red Derivative, (Trans, Trans)−1-Bromo-2,5-Bis-(3-Hydroxycarbonyl-4-Hydroxy)Styrylbenzene (BSB), Labels Diverse β-Pleated Sheet Structures in Postmortem Human Neurodegenerative Disease Brains

    PubMed Central

    Schmidt, Marie L.; Schuck, Theresa; Sheridan, Shelly; Kung, Mei-Ping; Kung, Hank; Zhuang, Zhi-Ping; Bergeron, Catherine; Lamarche, Jacque S.; Skovronsky, Daniel; Giasson, Benoit I.; Lee, Virginia M.-Y.; Trojanowski, John Q.

    2001-01-01

    A novel Congo red-derived fluorescent probe (trans, trans),−1-bromo-2,5-bis-(3-hydroxycarbonyl-4-hydroxy)styrylbenzene (BSB) that binds to amyloid plaques of postmortem Alzheimer’s disease brains and in transgenic mouse brains in vivo was designed as a prototype imaging agent for Alzheimer’s disease. In the current study, we used BSB to probe postmortem tissues from patients with various neurodegenerative diseases with diagnostic lesions characterized by fibrillar intra- or extracellular lesions and compared these results with standard histochemical dyes such as thioflavin S and immunohistochemical stains specific for the same lesions. These data show that BSB binds not only to extracellular amyloid β protein, but also many intracellular lesions composed of abnormal tau and synuclein proteins and suggests that radioiodinated BSB derivatives or related ligands may be useful imaging agents to monitor diverse amyloids in vivo. PMID:11549586

  15. Obesity is linked with lower brain volume in 700 AD and MCI patients

    PubMed Central

    Ho, April J.; Raji, Cyrus A.; Becker, James T.; Lopez, Oscar L.; Kuller, Lewis H.; Hua, Xue; Lee, Suh; Hibar, Derrek; Dinov, Ivo D.; Stein, Jason L.; Jack, Clifford R.; Weiner, Michael W.; Toga, Arthur W.; Thompson, Paul M.

    2011-01-01

    Obesity is associated with lower brain volumes in cognitively normal elderly subjects, but no study has yet investigated the effects of obesity on brain structure in patients with mild cognitive impairment (MCI) or Alzheimer’s disease (AD). To determine if higher body mass index (BMI) is associated with brain volume deficits in cognitively impaired elderly subjects, we analyzed brain magnetic resonance imaging (MRI) scans of 700 MCI or AD patients from two different cohorts: the Alzheimer’s Disease Neuroimaging Initiative (ADNI) and the Cardiovascular Health Study-Cognition Study (CHS-CS). Tensor-based morphometry (TBM) was used to create 3-dimensional maps of regional tissue excess or deficits in subjects with MCI (ADNI, N=399; CHS, N=77) and AD (ADNI, N=188; CHS, N=36). In both AD and MCI groups, higher BMI was associated with brain volume deficits in frontal, temporal, parietal, and occipital lobes; the atrophic pattern was consistent in both ADNI and CHS populations. Cardiovascular risk factors, especially obesity, should be considered as influencing brain structure in those already afflicted by cognitive impairment and dementia. PMID:20570405

  16. Postmortem examination of patient H.M.’s brain based on histological sectioning and digital 3D reconstruction

    NASA Astrophysics Data System (ADS)

    Annese, Jacopo; Schenker-Ahmed, Natalie M.; Bartsch, Hauke; Maechler, Paul; Sheh, Colleen; Thomas, Natasha; Kayano, Junya; Ghatan, Alexander; Bresler, Noah; Frosch, Matthew P.; Klaming, Ruth; Corkin, Suzanne

    2014-01-01

    Modern scientific knowledge of how memory functions are organized in the human brain originated from the case of Henry G. Molaison (H.M.), an epileptic patient whose amnesia ensued unexpectedly following a bilateral surgical ablation of medial temporal lobe structures, including the hippocampus. The neuroanatomical extent of the 1953 operation could not be assessed definitively during H.M.’s life. Here we describe the results of a procedure designed to reconstruct a microscopic anatomical model of the whole brain and conduct detailed 3D measurements in the medial temporal lobe region. This approach, combined with cellular-level imaging of stained histological slices, demonstrates a significant amount of residual hippocampal tissue with distinctive cytoarchitecture. Our study also reveals diffuse pathology in the deep white matter and a small, circumscribed lesion in the left orbitofrontal cortex. The findings constitute new evidence that may help elucidate the consequences of H.M.’s operation in the context of the brain’s overall pathology.

  17. Postmortem examination of patient H.M.’s brain based on histological sectioning and digital 3D reconstruction

    PubMed Central

    Annese, Jacopo; Schenker-Ahmed, Natalie M.; Bartsch, Hauke; Maechler, Paul; Sheh, Colleen; Thomas, Natasha; Kayano, Junya; Ghatan, Alexander; Bresler, Noah; Frosch, Matthew P.; Klaming, Ruth; Corkin, Suzanne

    2014-01-01

    Modern scientific knowledge of how memory functions are organized in the human brain originated from the case of Henry G. Molaison (H.M.), an epileptic patient whose amnesia ensued unexpectedly following a bilateral surgical ablation of medial temporal lobe structures, including the hippocampus. The neuroanatomical extent of the 1953 operation could not be assessed definitively during H.M.’s life. Here we describe the results of a procedure designed to reconstruct a microscopic anatomical model of the whole brain and conduct detailed 3D measurements in the medial temporal lobe region. This approach, combined with cellular-level imaging of stained histological slices, demonstrates a significant amount of residual hippocampal tissue with distinctive cytoarchitecture. Our study also reveals diffuse pathology in the deep white matter and a small, circumscribed lesion in the left orbitofrontal cortex. The findings constitute new evidence that may help elucidate the consequences of H.M.’s operation in the context of the brain’s overall pathology. PMID:24473151

  18. Is the solitary dark neuron a manifestation of postmortem trauma to the brain inadequately fixed by perfusion?

    PubMed

    Cammermeyer, J

    1978-06-01

    Dark neurons, classified as solitary because of their sparse occurrence, were discerned in the transitional zones between gray and white matter in various species of laboratory animals fixed by perfusion. These neurons, histologically indistinguishable from dark neurons in immersion fixed material, tended to develop when the saline perfusion was delayed or slow, the amount of the Bouin fixative was excessive, or the autopsy was performed shortly after the perfusion. Under these conditions, the white matter manifested a softer consistency and a paler color than the gray matter. These observations suggest that, as the consequence of regional differences in intensity and speed of fixation, distortion during extraction of the brain may activate a stress force in the transitional zones where incompletely fixed neurons become affected and acquire an abnormal affinity for aniline dyes and silver. PMID:97249

  19. FADD adaptor and PEA-15/ERK1/2 partners in major depression and schizophrenia postmortem brains: basal contents and effects of psychotropic treatments.

    PubMed

    García-Fuster, M J; Díez-Alarcia, R; Ferrer-Alcón, M; La Harpe, R; Meana, J J; García-Sevilla, J A

    2014-09-26

    Enhanced brain apoptosis (neurons and glia) may be involved in major depression (MD) and schizophrenia (SZ), mainly through the activation of the intrinsic (mitochondrial) apoptotic pathway. In the extrinsic death pathway, pro-apoptotic Fas-associated death domain (FADD) adaptor and its non-apoptotic p-Ser194 FADD form have critical roles interacting with other death regulators such as phosphoprotein enriched in astrocytes of 15 kDa (PEA-15) and extracellular signal-regulated kinase (ERK). The basal status of FADD (protein and messenger RNA (mRNA)) and the effects of psychotropic drugs (detected in blood/urine samples) were first assessed in postmortem prefrontal cortex of MD and SZ subjects (including a non-MD/SZ suicide group). In MD, p-FADD, but not total FADD (and mRNA), was increased (26%, n=24; all MD subjects) as well as p-FADD/FADD ratio (a pro-survival marker) in antidepressant-free MD subjects (50%, n=10). In contrast, cortical FADD (and mRNA), p-FADD, and p-FADD/FADD were not altered in SZ brains (n=21) regardless of antipsychotic medications (except enhanced mRNA in treated subjects). Similar negative results were quantified in the non-MD/SZ suicide group. In MD, the regulation of multifunctional PEA-15 (i.e., p-Ser116 PEA-15 blocks pro-apoptotic FADD and PEA-15 prevents pro-survival ERK action) and the modulation of p-ERK1/2 were also investigated. Cortical p-PEA-15 was not changed whereas PEA-15 was increased mainly in antidepressant-treated subjects (16-20%). Interestingly, cortical p-ERK1/2/ERK1/2 ratio was reduced (33%) in antidepressant-free when compared to antidepressant-treated MD subjects. The neurochemical adaptations of brain FADD (increased p-FADD and pro-survival p-FADD/FADD ratio), as well as its interaction with PEA-15, could play a major role to counteract the known activation of the mitochondrial apoptotic pathway in MD. PMID:25075716

  20. Abnormal activity of the MAPK- and cAMP-associated signaling pathways in frontal cortical areas in postmortem brain in schizophrenia.

    PubMed

    Funk, Adam J; McCullumsmith, Robert E; Haroutunian, Vahram; Meador-Woodruff, James H

    2012-03-01

    Recent evidence suggests that schizophrenia may result from alterations of integration of signaling mediated by multiple neurotransmitter systems. Abnormalities of associated intracellular signaling pathways may contribute to the pathophysiology of schizophrenia. Proteins and phospho-proteins comprising mitogen activated protein kinase (MAPK) and 3'-5'-cyclic adenosine monophosphate (cAMP)-associated signaling pathways may be abnormally expressed in the anterior cingulate (ACC) and dorsolateral prefrontal cortex (DLPFC) in schizophrenia. Using western blot analysis we examined proteins of the MAPK- and cAMP-associated pathways in these two brain regions. Postmortem samples were used from a well-characterized collection of elderly patients with schizophrenia (ACC=36, DLPFC=35) and a comparison (ACC=33, DLPFC=31) group. Near-infrared intensity of IR-dye labeled secondary antisera bound to targeted proteins of the MAPK- and cAMP-associated signaling pathways was measured using LiCor Odyssey imaging system. We found decreased expression of Rap2, JNK1, JNK2, PSD-95, and decreased phosphorylation of JNK1/2 at T183/Y185 and PSD-95 at S295 in the ACC in schizophrenia. In the DLPFC, we found increased expression of Rack1, Fyn, Cdk5, and increased phosphorylation of PSD-95 at S295 and NR2B at Y1336. MAPK- and cAMP-associated molecules constitute ubiquitous intracellular signaling pathways that integrate extracellular stimuli, modify receptor expression and function, and regulate cell survival and neuroplasticity. These data suggest abnormal activity of the MAPK- and cAMP-associated pathways in frontal cortical areas in schizophrenia. These alterations may underlie the hypothesized hypoglutamatergic function in this illness. Together with previous findings, these data suggest that abnormalities of intracellular signaling pathways may contribute to the pathophysiology of schizophrenia. PMID:22048463

  1. GABA-A and NMDA receptor subunit mRNA expression is altered in the caudate but not the putamen of the postmortem brains of alcoholics

    PubMed Central

    Bhandage, Amol K.; Jin, Zhe; Bazov, Igor; Kononenko, Olga; Bakalkin, Georgy; Korpi, Esa R.; Birnir, Bryndis

    2014-01-01

    Chronic consumption of alcohol by humans has been shown to lead to impairment of executive and cognitive functions. Here, we have studied the mRNA expression of ion channel receptors for glutamate and GABA in the dorsal striatum of post-mortem brains from alcoholics (n = 29) and normal controls (n = 29), with the focus on the caudate nucleus that is associated with the frontal cortex executive functions and automatic thinking and on the putamen area that is linked to motor cortices and automatic movements. The results obtained by qPCR assay revealed significant changes in the expression of specific excitatory ionotropic glutamate and inhibitory GABA-A receptor subunit genes in the caudate but not the putamen. Thus, in the caudate we found reduced levels of mRNAs encoding the GluN2A glutamate receptor and the δ, ε, and ρ2 GABA-A receptor subunits, and increased levels of the mRNAs encoding GluD1, GluD2, and GABA-A γ1 subunits in the alcoholics as compared to controls. Interestingly in the controls, 11 glutamate and 5 GABA-A receptor genes were more prominently expressed in the caudate than the putamen (fold-increase varied from 1.24 to 2.91). Differences in gene expression patterns between the striatal regions may underlie differences in associated behavioral outputs. Our results suggest an altered balance between caudate-mediated voluntarily controlled and automatic behaviors in alcoholics, including diminished executive control on goal-directed alcohol-seeking behavior. PMID:25538565

  2. Neurodegeneration and Alzheimer's disease (AD). What Can Proteomics Tell Us About the Alzheimer's Brain?

    PubMed

    Moya-Alvarado, Guillermo; Gershoni-Emek, Noga; Perlson, Eran; Bronfman, Francisca C

    2016-02-01

    Neurodegenerative diseases, such as Alzheimer's diseases (AD), are becoming more prevalent as the population ages. However, the mechanisms that lead to synapse destabilization and neuron death remain elusive. The advent of proteomics has allowed for high-throughput screening methods to search for biomarkers that could lead to early diagnosis and treatment and to identify alterations in the cellular proteome that could provide insight into disease etiology and possible treatment avenues. In this review, we have concentrated mainly on the findings that are related to how and whether proteomics studies have contributed to two aspects of AD research, the development of biomarkers for clinical diagnostics, and the recognition of proteins that can help elucidate the pathways leading to AD brain pathology. As a result of these studies, several candidate cerebrospinal fluid biomarkers are now available for further validation in different AD cohorts. Studies in AD brain and AD transgenic models support the notion that oxidative damage results in the alterations of metabolic enzymes and that mitochondrial dysfunction is central to AD neuropathology. PMID:26657538

  3. Study of amyloid-β peptide functional brain networks in AD, MCI and HC.

    PubMed

    Jiang, Jiehui; Duan, Huoqiang; Huang, Zheming; Yu, Zhihua

    2015-01-01

    One medical challenge in studying the amyloid-β (Aβ) peptide mechanism for Alzheimer's disease (AD) is exploring the law of beta toxic oligomers' diffusion in human brains in vivo. One beneficial means of solving this problem is brain network analysis based on graph theory. In this study, the characteristics of Aβ functional brain networks of Healthy Control (HC), Mild Cognitive Impairment (MCI), and AD groups were compared by applying graph theoretical analyses to Carbon 11-labeled Pittsburgh compound B positron emission tomography (11C PiB-PET) data. 120 groups of PiB-PET images from the ADNI database were analyzed. The results showed that the small-world property of MCI and AD were lost as compared to HC. Furthermore, the local clustering of networks was higher in both MCI and AD as compared to HC, whereas the path length was similar among the three groups. The results also showed that there could be four potential Aβ toxic oligomer seeds: Frontal_Sup_Medial_L, Parietal_Inf_L, Frontal_Med_Orb_R, and Parietal_Inf_R. These four seeds are corresponding to Regions of Interests referred by physicians to clinically diagnose AD. PMID:26405999

  4. Vascular risk and Aβ interact to reduce cortical thickness in AD vulnerable brain regions

    PubMed Central

    Reed, Bruce R.; Madison, Cindee M.; Wirth, Miranka; Marchant, Natalie L.; Kriger, Stephen; Mack, Wendy J.; Sanossian, Nerses; DeCarli, Charles; Chui, Helena C.; Weiner, Michael W.; Jagust, William J.

    2014-01-01

    Objective: The objective of this study was to define whether vascular risk factors interact with β-amyloid (Aβ) in producing changes in brain structure that could underlie the increased risk of Alzheimer disease (AD). Methods: Sixty-six cognitively normal and mildly impaired older individuals with a wide range of vascular risk factors were included in this study. The presence of Aβ was assessed using [11C]Pittsburgh compound B–PET imaging, and cortical thickness was measured using 3-tesla MRI. Vascular risk was measured with the Framingham Coronary Risk Profile Index. Results: Individuals with high levels of vascular risk factors have thinner frontotemporal cortex independent of Aβ. These frontotemporal regions are also affected in individuals with Aβ deposition, but the latter show additional thinning in parietal cortices. Aβ and vascular risk were found to interact in posterior (especially in parietal) brain regions, where Aβ has its greatest effect. In this way, the negative effect of Aβ in posterior regions is increased by the presence of vascular risk. Conclusion: Aβ and vascular risk interact to enhance cortical thinning in posterior brain regions that are particularly vulnerable to AD. These findings give insight concerning the mechanisms whereby vascular risk increases the likelihood of developing AD and supports the therapeutic intervention of controlling vascular risk for the prevention of AD. PMID:24907234

  5. [Late-onset Neurodegenerative Diseases Following Traumatic Brain Injury: Chronic Traumatic Encephalopathy (CTE) and Alzheimer's Disease Secondary to TBI (AD-TBI)].

    PubMed

    Takahata, Keisuke; Tabuchi, Hajime; Mimura, Masaru

    2016-07-01

    Chronic traumatic encephalopathy (CTE) is a neurodegenerative disease, which is associated with mild repetitive traumatic brain injury (TBI). This long-term and progressive symptom due to TBI was initially called punch-drunk syndrome or dementia pugilistica, since it was believed to be associated with boxing. However, serial neuropathological studies of mild repetitive TBI in the last decade have revealed that CTE occurs not only in boxers but also in a wider population including American football players, wrestlers, and military personnel. CTE has gained large public interest owing to dramatic cases involving retired professional athletes wherein serious behavioral problems and tragic incidents were reported. Unlike mild repetitive TBI, a single episode of severe TBI can cause another type of late-onset neuropsychiatric disease including Alzheimer's disease (AD). Several epidemiological studies have shown that a single episode of severe TBI is one of the major risk factors of AD. Pathologically, both AD and CTE are characterized by abnormal accumulations of hyperphosphorylated tau proteins. However, recent neuropathological studies revealed that CTE demonstrates a unique pattern of tau pathology in neurons and astrocytes, and accumulation of other misfolded proteins such as TDP-43. Currently, no reliable biomarkers of late-onset neurodegenerative diseases following TBI are available, and a definitive diagnosis can be made only via postmortem neuropathological examination. Development in neuroimaging techniques such as tau and amyloid positron emission tomography imaging might not only enable early diagnosis of CTE, but also contribute to the interventions for prevention of late-onset neurodegenerative diseases following TBI. Further studies are necessary to elucidate the mechanisms of neurodegeneration in the living brain of patients with TBI. PMID:27395469

  6. Functional Analysis of Genetic Variation in Catechol-O-Methyltransferase (COMT): Effects on mRNA, Protein, and Enzyme Activity in Postmortem Human Brain

    PubMed Central

    Chen, Jingshan; Lipska, Barbara K.; Halim, Nader; Ma, Quang D.; Matsumoto, Mitsuyuki; Melhem, Samer; Kolachana, Bhaskar S.; Hyde, Thomas M.; Herman, Mary M.; Apud, Jose; Egan, Michael F.; Kleinman, Joel E.; Weinberger, Daniel R.

    2004-01-01

    Catechol-O-methyltransferase (COMT) is a key enzyme in the elimination of dopamine in the prefrontal cortex of the human brain. Genetic variation in the COMT gene (MIM 116790) has been associated with altered prefrontal cortex function and higher risk for schizophrenia, but the specific alleles and their functional implications have been controversial. We analyzed the effects of several single-nucleotide polymorphisms (SNPs) within COMT on mRNA expression levels (using reverse-transcriptase polymerase chain reaction analysis), protein levels (using Western blot analysis), and enzyme activity (using catechol methylation) in a large sample (n = 108) of postmortem human prefrontal cortex tissue, which predominantly expresses the -membrane-bound isoform. A common coding SNP, Val158Met (rs4680), significantly affected protein abundance and enzyme activity but not mRNA expression levels, suggesting that differences in protein integrity account for the difference in enzyme activity between alleles. A SNP in intron 1 (rs737865) and a SNP in the 3′ flanking region (rs165599)—both of which have been reported to contribute to allelic expression differences and to be associated with schizophrenia as part of a haplotype with Val—had no effect on mRNA expression levels, protein immunoreactivity, or enzyme activity. In lymphocytes from 47 subjects, we confirmed a similar effect on enzyme activity in samples with the Val/Met genotype but no effect in samples with the intron 1 or 3′ SNPs. Separate analyses revealed that the subject's sex, as well as the presence of a SNP in the P2 promoter region (rs2097603), had small effects on COMT enzyme activity. Using site-directed mutagenesis of mouse COMT cDNA, followed by in vitro translation, we found that the conversion of Leu at the homologous position into Met or Val progressively and significantly diminished enzyme activity. Thus, although we cannot exclude a more complex genetic basis for functional effects of COMT, Val is a

  7. Brain areas involved in the acupuncture treatment of AD model rats: a PET study

    PubMed Central

    2014-01-01

    Background Acupuncture may effectively treat certain symptoms of Alzheimer’s disease (AD). Although several studies have used functional brain imaging to investigate the mechanisms of acupuncture treatment on AD, these mechanisms are still poorly understood. We therefore further explored the mechanism by which needling at ST36 may have a therapeutic effect in a rat AD model. Methods A total of 80 healthy Wistar rats were divided into healthy control (n = 15) and pre-model (n = 65) groups. After inducing AD-like disease, a total of 45 AD model rats were randomly divided into three groups: the model group (n = 15), the sham-point group (n = 15), and the ST36 group (n = 15). The above three groups underwent PET scanning. PET images were processed with SPM2. Results The brain areas that were activated in the sham-point group relative to the model group were primarily centred on the bilateral limbic system, the right frontal lobe, and the striatum, whereas the activated areas in the ST36 group were primarily centred on the bilateral limbic system (pyriform cortex), the bilateral temporal lobe (olfactory cortex), the right amygdala and the right hippocampus. Compared with the sham-point group, the ST36 group showed greater activation in the bilateral amygdalae and the left temporal lobe. Conclusion We concluded that needling at a sham point or ST36 can increase blood perfusion and glycol metabolism in certain brain areas, and thus may have a positive influence on the cognition of AD patients. PMID:24886495

  8. Brain cholinesterases: III. Future perspectives of AD research and clinical practice.

    PubMed

    Shen, Z-X

    2004-01-01

    Alzheimer's disease (AD) is initially and primarily associated with the degeneration and alteration in the metabolism of cholinesterases (ChEs). The use of ChEs inhibitors to treat Alzheimer's condition, on the basis of the cholinergic hypothesis of the disease, is, therefore, without grounds. Most disturbing is the fact that the currently available anti-ChEs are designed to inhibit normal ChEs in the brain and throughout the body, but not the abnormal ones. Based on the acetylcholinesterase (AChE) deficiency theory, treatment should be designed to protect the cranial ChEs system from alteration and/or to help that system fight against degeneration through restoring its homeostatic action for brain structure and function instead. The overlap in the clinical, biochemical, molecular-cellular, and pathological alterations seen in patients with AD and individuals with many other brain disorders, which has bewildered many investigators, may now be explained by the shared underlying mismetabolism of brain ChEs. The abnormal metabolism of ChEs existing in asymptomatic subjects may indicate that the system is "at risk" and deserves serious attention. Future perspectives of ChEs research in vivo and in vitro in connection with AD and clinical diagnosis, prevention and treatment are proposed. Several potentially useful therapeutic and preventive means and pharmacological agents in this regard are identified and discussed, such as physical and intellectual stimulation, and a class of drugs including vitamin E, R-(-)-deprenyl (deprenyl, selegiline), acetyl L-carnitine, cytidine diphosphocholine (CDP-choline), centrophenoxine, L-phenylalanine, naloxone, galactose, and lithium, that have been proven to be able to stimulate AChE activity. Their working mechanisms may be through directly changing the configuration of AChE molecules and/or correcting micro- and overall environmental biological conditions for ChEs. PMID:15236794

  9. Postmortem biochemistry: Current applications.

    PubMed

    Belsey, S L; Flanagan, R J

    2016-07-01

    The results of biochemical analyses in specimens obtained postmortem may aid death investigation when diabetic and alcoholic ketoacidosis is suspected, when death may have been the result of drowning, anaphylaxis, or involved a prolonged stress response such as hypothermia, and in the diagnosis of disease processes such as inflammation, early myocardial infarction, or sepsis. There is often cross-over with different disciplines, in particular with clinical and forensic toxicology, since some endogenous substances such as sodium chloride, potassium chloride, and insulin can be used as poisons. The interpretation of results is often complicated because of the likelihood of postmortem change in analyte concentration or activity, and proper interpretation must take into account all the available evidence. The unpredictability of postmortem changes means that use of biochemical measurements in time of death estimation has little value. The use of vitreous humour is beneficial for many analytes as the eye is in a physically protected environment, this medium may be less affected by autolysis or microbial metabolism than blood, and the assays can be performed with due precaution using standard clinical chemistry analysers. However, interpretation of results may not be straightforward because (i) defined reference ranges in life are often lacking, (ii) there is a dearth of knowledge regarding, for example, the speed of equilibration of many analytes between blood, vitreous humour, and other fluids that may be sampled, and (iii) the effects of post-mortem change are difficult to quantify because of the lack of control data. A major limitation is that postmortem vitreous glucose measurements are of no help in diagnosing antemortem hypoglycaemia. PMID:27131037

  10. Predicting conversion from MCI to AD with FDG-PET brain images at different prodromal stages.

    PubMed

    Cabral, Carlos; Morgado, Pedro M; Campos Costa, Durval; Silveira, Margarida

    2015-03-01

    Early diagnosis of Alzheimer disease (AD), while still at the stage known as mild cognitive impairment (MCI), is important for the development of new treatments. However, brain degeneration in MCI evolves with time and differs from patient to patient, making early diagnosis a very challenging task. Despite these difficulties, many machine learning techniques have already been used for the diagnosis of MCI and for predicting MCI to AD conversion, but the MCI group used in previous works is usually very heterogeneous containing subjects at different stages. The goal of this paper is to investigate how the disease stage impacts on the ability of machine learning methodologies to predict conversion. After identifying the converters and estimating the time of conversion (TC) (using neuropsychological test scores), we devised 5 subgroups of MCI converters (MCI-C) based on their temporal distance to the conversion instant (0, 6, 12, 18 and 24 months before conversion). Next, we used the FDG-PET images of these subgroups and trained classifiers to distinguish between the MCI-C at different stages and stable non-converters (MCI-NC). Our results show that MCI to AD conversion can be predicted as early as 24 months prior to conversion and that the discriminative power of the machine learning methods decreases with the increasing temporal distance to the TC, as expected. These findings were consistent for all the tested classifiers. Our results also show that this decrease arises from a reduction in the information contained in the regions used for classification and by a decrease in the stability of the automatic selection procedure. PMID:25625698

  11. Association analysis of the DISC1 gene with schizophrenia in the Japanese population and DISC1 immunoreactivity in the postmortem brain.

    PubMed

    Ratta-Apha, Woraphat; Hishimoto, Akitoyo; Mouri, Kentaro; Shiroiwa, Kyoichi; Sasada, Toru; Yoshida, Masakuni; Supriyanto, Irwan; Ueno, Yasuhiro; Asano, Migiwa; Shirakawa, Osamu; Togashi, Hideru; Takai, Yoshimi; Sora, Ichiro

    2013-12-01

    The Disrupted-in-Schizophrenia 1 (DISC1) gene plays a role in the regulation of neural development. Previous evidence from genetic association and biological studies implicates the DISC1 gene as having a role in the pathophysiology of schizophrenia. In the present study, we explored the association between DISC1 missense mutation rs821616 (Ser704Cys) single nucleotide polymorphism (SNP) and four other SNPs (rs1772702, rs1754603, rs821621, rs821624) in the related haplotype block and schizophrenia in the Japanese population. We could not find a significant association of selected SNPs with schizophrenia after correction for multiple testing. We performed a meta-analysis of the Ser704Cys variant in schizophrenia using data from the present study and five previous Japanese population studies, and found no association with schizophrenia. We also examined DISC1 immunoreactivity in postmortem prefrontal cortex specimens of schizophrenia patients compared to control samples. The immunoreactivity revealed a significant decrease of DISC1 protein expression in the schizophrenia samples after ruling out potential confounding factors. However, the Ser704Cys variant did not show effects on DISC1 immunoreactivity. These results provide evidence that this functional genetic variation of DISC1 do not underlie the pathophysiology of schizophrenia in the Japanese population. PMID:24013095

  12. Validation of adequate endogenous reference genes for reverse transcription-qPCR studies in human post-mortem brain tissue of SIDS cases.

    PubMed

    El-Kashef, Noha; Gomes, Iva; Mercer-Chalmers-Bender, Katja; Schneider, Peter M; Rothschild, Markus A; Juebner, Martin

    2015-12-01

    Sudden infant death syndrome (SIDS) is the main cause of post-neonatal infant death in most developed countries. It is still of ambiguous etiology. Gene expression studies of relevant target genes using reverse transcription quantitative real-time PCR (RT-qPCR) in SIDS cases, and comparing them with age-matched controls, could help in understanding the pathogenesis of SIDS. However, selecting inadequate reference genes used for normalization of the RT-qPCR gene expression data can give misleading results. The aim of the present study was to identify reference genes with the most stable expression in post-mortem brainstem samples of SIDS and control cases. Among the five candidate reference genes (GAPDH, GUSB, HMBS, SDHA, UBXN6) studied in both groups, SDHA and UBXN6 were identified as the most stable. To further demonstrate the importance of using validated genes for RT-qPCR data normalization, the expression of a potential gene of interest in SIDS, the RPS27A gene, was evaluated using validated versus non-validated reference genes for normalization. This gene encodes the ubiquitin protein that has been shown in other pathological studies to be induced in SIDS. Using the identified most stable genes for normalization of RPS27A gene expression data revealed, as expected, a statistically significant up-regulation in SIDS as compared to the controls. However, using a single unstable reference gene for normalization resulted in no significant differences in transcript abundance of RPS27A between SIDS and the controls. This emphasizes the need for validation of the suitability of reference genes used in a given tissue type under certain experimental conditions. PMID:26434654

  13. Decrease of mGluR5 receptor density goes parallel with changes in enkephalin and substance P immunoreactivity in Huntington's disease: a preliminary investigation in the postmortem human brain.

    PubMed

    Gulyás, Balázs; Sovago, Judit; Gomez-Mancilla, Baltazar; Jia, Zhisheng; Szigeti, Csaba; Gulya, Károly; Schumacher, Martin; Maguire, Ralph Paul; Gasparini, Fabrizio; Halldin, Christer

    2015-09-01

    Group 1 metabotropic glutamate subtype 5 receptors (mGluR5) contribute to the control of motor behavior by regulating the balance between excitation and inhibition of outputs in the basal ganglia. The density of these receptors is increased in patients with Parkinson's disease and motor complications. We hypothesized that similar changes may occur in Huntington's disease (HD) and aimed at testing this hypothesis in a preliminary experimental series in postmortem human brain material obtained from HD patients. Using autoradiography, we analyzed mGluR5 density in the putamen, caudate nucleus and cerebellum (control region) in postmortem tissue samples from three patients with HD and three controls with two mGluR5-specific radioligands ([(3)H]ABP688 and [(11)C]ABP688). The density of enkephalin (Enk)- or substance P (SP)-containing neurons was assessed using immunohistochemical and cell-counting methods. [(3)H]ABP688 binding in HD was reduced in the caudate (-70.4 %, P < 0.001), in the putamen (-33.3 %, P = 0.053), and in the cerebellum (-8.79 %, P = 0.930) vs controls. Results with [(11)C]ABP688 were similar; there was good correlation between [(11)C]ABP688 and [(3)H]ABP688 binding ratios. Total cell density was similar in all three brain regions in HD patients and controls. Neuronal density was 69 % lower in the caudate (P = 0.002) and 64 % lower in the putamen (P < 0.001) of HD patients vs controls. Both direct and indirect pathways were affected, with ≥ 90 % decrease in the density of Enk- and SP-containing neurons in the caudate and putamen of HD patients vs controls (P < 0.001). In contrast to earlier observations in PD, in HD, compared to controls, the mGluR5 density was significantly lower in the caudate nucleus. The decrease in neuronal density suggests that neuronal loss was largely responsible for the observed decrease in mGluR5. PMID:24969128

  14. Quantitative measurement of intact alpha-synuclein proteoforms from post-mortem control and Parkinson's disease brain tissue by intact protein mass spectrometry.

    PubMed

    Kellie, John F; Higgs, Richard E; Ryder, John W; Major, Anthony; Beach, Thomas G; Adler, Charles H; Merchant, Kalpana; Knierman, Michael D

    2014-01-01

    A robust top down proteomics method is presented for profiling alpha-synuclein species from autopsied human frontal cortex brain tissue from Parkinson's cases and controls. The method was used to test the hypothesis that pathology associated brain tissue will have a different profile of post-translationally modified alpha-synuclein than the control samples. Validation of the sample processing steps, mass spectrometry based measurements, and data processing steps were performed. The intact protein quantitation method features extraction and integration of m/z data from each charge state of a detected alpha-synuclein species and fitting of the data to a simple linear model which accounts for concentration and charge state variability. The quantitation method was validated with serial dilutions of intact protein standards. Using the method on the human brain samples, several previously unreported modifications in alpha-synuclein were identified. Low levels of phosphorylated alpha synuclein were detected in brain tissue fractions enriched for Lewy body pathology and were marginally significant between PD cases and controls (p = 0.03). PMID:25052239

  15. Quantitative Measurement of Intact Alpha-Synuclein Proteoforms from Post-Mortem Control and Parkinson's Disease Brain Tissue by Intact Protein Mass Spectrometry

    PubMed Central

    Kellie, John F.; Higgs, Richard E.; Ryder, John W.; Major, Anthony; Beach, Thomas G.; Adler, Charles H.; Merchant, Kalpana; Knierman, Michael D.

    2014-01-01

    A robust top down proteomics method is presented for profiling alpha-synuclein species from autopsied human frontal cortex brain tissue from Parkinson's cases and controls. The method was used to test the hypothesis that pathology associated brain tissue will have a different profile of post-translationally modified alpha-synuclein than the control samples. Validation of the sample processing steps, mass spectrometry based measurements, and data processing steps were performed. The intact protein quantitation method features extraction and integration of m/z data from each charge state of a detected alpha-synuclein species and fitting of the data to a simple linear model which accounts for concentration and charge state variability. The quantitation method was validated with serial dilutions of intact protein standards. Using the method on the human brain samples, several previously unreported modifications in alpha-synuclein were identified. Low levels of phosphorylated alpha synuclein were detected in brain tissue fractions enriched for Lewy body pathology and were marginally significant between PD cases and controls (p = 0.03). PMID:25052239

  16. Quantitative Measurement of Intact Alpha-Synuclein Proteoforms from Post-Mortem Control and Parkinson's Disease Brain Tissue by Intact Protein Mass Spectrometry

    NASA Astrophysics Data System (ADS)

    Kellie, John F.; Higgs, Richard E.; Ryder, John W.; Major, Anthony; Beach, Thomas G.; Adler, Charles H.; Merchant, Kalpana; Knierman, Michael D.

    2014-07-01

    A robust top down proteomics method is presented for profiling alpha-synuclein species from autopsied human frontal cortex brain tissue from Parkinson's cases and controls. The method was used to test the hypothesis that pathology associated brain tissue will have a different profile of post-translationally modified alpha-synuclein than the control samples. Validation of the sample processing steps, mass spectrometry based measurements, and data processing steps were performed. The intact protein quantitation method features extraction and integration of m/z data from each charge state of a detected alpha-synuclein species and fitting of the data to a simple linear model which accounts for concentration and charge state variability. The quantitation method was validated with serial dilutions of intact protein standards. Using the method on the human brain samples, several previously unreported modifications in alpha-synuclein were identified. Low levels of phosphorylated alpha synuclein were detected in brain tissue fractions enriched for Lewy body pathology and were marginally significant between PD cases and controls (p = 0.03).

  17. Postmortem evidence of cerebral inflammation in schizophrenia: a systematic review

    PubMed Central

    Trépanier, M O; Hopperton, K E; Mizrahi, R; Mechawar, N; Bazinet, R P

    2016-01-01

    Schizophrenia is a psychiatric disorder which has a lifetime prevalence of ~1%. Multiple candidate mechanisms have been proposed in the pathogenesis of schizophrenia. One such mechanism is the involvement of neuroinflammation. Clinical studies, including neuroimaging, peripheral biomarkers and randomized control trials, have suggested the presence of neuroinflammation in schizophrenia. Many studies have also measured markers of neuroinflammation in postmortem brain samples from schizophrenia patients. The objective of this study was to conduct a systematic search of the literature on neuroinflammation in postmortem brains of schizophrenia patients indexed in MEDLINE, Embase and PsycINFO. Databases were searched up until 20th March 2016 for articles published on postmortem brains in schizophrenia evaluating microglia, astrocytes, glia, cytokines, the arachidonic cascade, substance P and other markers of neuroinflammation. Two independent reviewers extracted the data. Out of 5385 articles yielded by the search, 119 articles were identified that measured neuroinflammatory markers in schizophrenic postmortem brains. Glial fibrillary acidic protein expression was elevated, lower or unchanged in 6, 6 and 21 studies, respectively, and similar results were obtained for glial cell densities. On the other hand, microglial markers were increased, lower or unchanged in schizophrenia in 11, 3 and 8 studies, respectively. Results were variable across all other markers, but SERPINA3 and IFITM were consistently increased in 4 and 5 studies, respectively. Despite the variability, some studies evaluating neuroinflammation in postmortem brains in schizophrenia suggest an increase in microglial activity and other markers such as SERPINA3 and IFITM. Variability across studies is partially explained by multiple factors including brain region evaluated, source of the brain, diagnosis, age at time of death, age of onset and the presence of suicide victims in the cohort. PMID:27271499

  18. Postmortem evidence of cerebral inflammation in schizophrenia: a systematic review.

    PubMed

    Trépanier, M O; Hopperton, K E; Mizrahi, R; Mechawar, N; Bazinet, R P

    2016-08-01

    Schizophrenia is a psychiatric disorder which has a lifetime prevalence of ~1%. Multiple candidate mechanisms have been proposed in the pathogenesis of schizophrenia. One such mechanism is the involvement of neuroinflammation. Clinical studies, including neuroimaging, peripheral biomarkers and randomized control trials, have suggested the presence of neuroinflammation in schizophrenia. Many studies have also measured markers of neuroinflammation in postmortem brain samples from schizophrenia patients. The objective of this study was to conduct a systematic search of the literature on neuroinflammation in postmortem brains of schizophrenia patients indexed in MEDLINE, Embase and PsycINFO. Databases were searched up until 20th March 2016 for articles published on postmortem brains in schizophrenia evaluating microglia, astrocytes, glia, cytokines, the arachidonic cascade, substance P and other markers of neuroinflammation. Two independent reviewers extracted the data. Out of 5385 articles yielded by the search, 119 articles were identified that measured neuroinflammatory markers in schizophrenic postmortem brains. Glial fibrillary acidic protein expression was elevated, lower or unchanged in 6, 6 and 21 studies, respectively, and similar results were obtained for glial cell densities. On the other hand, microglial markers were increased, lower or unchanged in schizophrenia in 11, 3 and 8 studies, respectively. Results were variable across all other markers, but SERPINA3 and IFITM were consistently increased in 4 and 5 studies, respectively. Despite the variability, some studies evaluating neuroinflammation in postmortem brains in schizophrenia suggest an increase in microglial activity and other markers such as SERPINA3 and IFITM. Variability across studies is partially explained by multiple factors including brain region evaluated, source of the brain, diagnosis, age at time of death, age of onset and the presence of suicide victims in the cohort. PMID:27271499

  19. Decreased calcineurin immunoreactivity in the postmortem brain of a patient with schizophrenia who had been prescribed the calcineurin inhibitor, tacrolimus, for leukemia

    PubMed Central

    Wada, Akira; Kunii, Yasuto; Matsumoto, Jyunya; Hino, Mizuki; Nagaoka, Atsuko; Niwa, Shin-ichi; Yabe, Hirooki

    2016-01-01

    Background The calcineurin (CaN) inhibitor, tacrolimus, is widely used in patients undergoing allogeneic organ transplantation and in those with certain allergic diseases. Recently, several reports have suggested that CaN is also associated with schizophrenia. However, little data are currently available on the direct effect of tacrolimus on the human brain. Case A 23-year-old Japanese female experienced severe delusion of persecution, delusional mood, suspiciousness, aggression, and excitement. She visited our hospital and was diagnosed with schizophrenia. When she was 27 years old, she had severe general fatigue, persistent fever, systemic joint pain, gingival bleeding, and breathlessness and was diagnosed with acute myelomonocytic leukemia. Later she underwent bone marrow transplantation (BMT), she was administered methotrexate and cyclosporin A to prevent graft versus host disease (GVHD). Three weeks after BMT, she showed initial symptoms of GVHD and was prescribed tacrolimus instead of cyclosporin A. Seven months after BMT at the age of 31 years, she died of progression of GVHD. Pathological anatomy was examined after her death, including immunohistochemical analysis of her brain using anti-CaN antibodies. For comparison, we used our previous data from both a schizophrenia group and a healthy control group. No significant differences were observed in the percentage of CaN-immunoreactive neurons among the schizophrenia group, healthy control group, and the tacrolimus case (all P>0.5, analysis of covariance). Compared with the healthy control group and schizophrenia group, the percentages of CaN-immunoreactive neurons in layers III–VI of the BA46 and the putamen tended to be lower in the tacrolimus case. Conclusion Tacrolimus may decrease CaN immunoreactivity in some regions of the human brain. Thus, tacrolimus may introduce side effects such as cognitive dysfunction and extrapyramidal symptoms. In addition, we also found that the effect of tacrolimus on Ca

  20. Modulation in Activation and Expression of PTEN, Akt1, and PDK1: Further Evidence Demonstrating Altered Phosphoinositide 3-kinase Signaling in Postmortem Brain of Suicide Subjects

    PubMed Central

    Dwivedi, Yogesh; Rizavi, Hooriyah S.; Zhang, Hui; Roberts, Rosalinda C.; Conley, Robert R.; Pandey, Ghanshyam N.

    2010-01-01

    Background Phosphoinositide 3-kinase (PI 3-K) signaling plays a crucial role in neuronal growth and plasticity. Recently, we demonstrated that suicide brain is associated with decreased activation and expression of selective catalytic and regulatory subunits of PI 3-K. The present investigation examined the regulation and functional significance of compromised PI 3-K in suicide brain at the level of upstream phosphatase and tensin homolog on chromosome ten (PTEN) and downstream substrates 3-phosphoinositide-dependent kinase 1 (PDK1) and Akt. Method mRNA expression of Akt1, Akt3, PTEN, and PDK1 by competitive RT-PCR; protein expression of Akt1, Akt3, PTEN, PDK1, phosphorylated-Akt1 (Ser473), phosphorylated-Akt1(Thr308), phosphorylated-PDK1, and phosphorylated-PTEN by Western blot; and catalytic activities of Akt1, Akt3, and PDK1 by enzymatic assays were determined in prefrontal cortex (PFC) and hippocampus obtained from suicide subjects and nonpsychiatric controls. Results No significant changes in the expression of Akt1 or Akt3 were observed; however, catalytic activity of Akt1, but not of Akt3, was decreased in PFC and hippocampus of suicide subjects, which was associated with decreased phosphorylation of Akt1 at Ser473 and Thr308. The catalytic activity of PDK1 and the level of phosphorylated-PDK1 were also decreased in both brain areas without any change in expression levels of PDK1. On the other hand, mRNA and protein expression of PTEN was increased, whereas the level of phosphorylated-PTEN was decreased. Conclusion Our study demonstrates abnormalities in PI 3-K signaling at several levels in brain of suicide subjects and suggests the possible involvement of aberrant PI 3-K/Akt signaling in the pathogenic mechanisms of suicide. PMID:20163786

  1. Evaluation of post-mortem lateral cerebral ventricle changes using sequential scans during post-mortem computed tomography.

    PubMed

    Hasegawa, Iwao; Shimizu, Akinobu; Saito, Atsushi; Suzuki, Hideto; Vogel, Hermann; Püschel, Klaus; Heinemann, Axel

    2016-09-01

    In the present study, we evaluated post-mortem lateral cerebral ventricle (LCV) changes using computed tomography (CT). Subsequent periodical CT scans termed "sequential scans" were obtained for three cadavers. The first scan was performed immediately after the body was transferred from the emergency room to the institute of legal medicine. Sequential scans were obtained and evaluated for 24 h at maximum. The time of death had been determined in the emergency room. The sequential scans enabled us to observe periodical post-mortem changes in CT images. The series of continuous LCV images obtained up to 24 h (two cases)/16 h (1 case) after death was evaluated. The average Hounsfield units (HU) within the LCVs progressively increased, and LCV volume progressively decreased over time. The HU in the cerebrospinal fluid (CSF) increased at an individual rate proportional to the post-mortem interval (PMI). Thus, an early longitudinal radiodensity change in the CSF could be potential indicator of post-mortem interval (PMI). Sequential imaging scans reveal post-mortem changes in the CSF space which may reflect post-mortem brain alterations. Further studies are needed to evaluate the proposed CSF change markers in correlation with other validated PMI indicators. PMID:27048214

  2. Considerations in establishing a post-mortem brain and tissue bank for the study of myalgic encephalomyelitis/chronic fatigue syndrome: a proposed protocol

    PubMed Central

    2014-01-01

    Background Our aim, having previously investigated through a qualitative study involving extensive discussions with experts and patients the issues involved in establishing and maintaining a disease specific brain and tissue bank for myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), was to develop a protocol for a UK ME/CFS repository of high quality human tissue from well characterised subjects with ME/CFS and controls suitable for a broad range of research applications. This would involve a specific donor program coupled with rapid tissue collection and processing, supplemented by comprehensive prospectively collected clinical, laboratory and self-assessment data from cases and controls. Findings We reviewed the operations of existing tissue banks from published literature and from their internal protocols and standard operating procedures (SOPs). On this basis, we developed the protocol presented here, which was designed to meet high technical and ethical standards and legal requirements and was based on recommendations of the MRC UK Brain Banks Network. The facility would be most efficient and cost-effective if incorporated into an existing tissue bank. Tissue collection would be rapid and follow robust protocols to ensure preservation sufficient for a wide range of research uses. A central tissue bank would have resources both for wide-scale donor recruitment and rapid response to donor death for prompt harvesting and processing of tissue. Conclusion An ME/CFS brain and tissue bank could be established using this protocol. Success would depend on careful consideration of logistic, technical, legal and ethical issues, continuous consultation with patients and the donor population, and a sustainable model of funding ideally involving research councils, health services, and patient charities. This initiative could revolutionise the understanding of this still poorly-understood disease and enhance development of diagnostic biomarkers and treatments

  3. Analysis of YFP(J16)-R6/2 reporter mice and postmortem brains reveals early pathology and increased vulnerability of callosal axons in Huntington's disease.

    PubMed

    Gatto, Rodolfo G; Chu, Yaping; Ye, Allen Q; Price, Steven D; Tavassoli, Ehsan; Buenaventura, Andrea; Brady, Scott T; Magin, Richard L; Kordower, Jeffrey H; Morfini, Gerardo A

    2015-09-15

    Cumulative evidence indicates that the onset and severity of Huntington's disease (HD) symptoms correlate with connectivity deficits involving specific neuronal populations within cortical and basal ganglia circuits. Brain imaging studies and pathological reports further associated these deficits with alterations in cerebral white matter structure and axonal pathology. However, whether axonopathy represents an early pathogenic event or an epiphenomenon in HD remains unknown, nor is clear the identity of specific neuronal populations affected. To directly evaluate early axonal abnormalities in the context of HD in vivo, we bred transgenic YFP(J16) with R6/2 mice, a widely used HD model. Diffusion tensor imaging and fluorescence microscopy studies revealed a marked degeneration of callosal axons long before the onset of motor symptoms. Accordingly, a significant fraction of YFP-positive cortical neurons in YFP(J16) mice cortex were identified as callosal projection neurons. Callosal axon pathology progressively worsened with age and was influenced by polyglutamine tract length in mutant huntingtin (mhtt). Degenerating axons were dissociated from microscopically visible mhtt aggregates and did not result from loss of cortical neurons. Interestingly, other axonal populations were mildly or not affected, suggesting differential vulnerability to mhtt toxicity. Validating these results, increased vulnerability of callosal axons was documented in the brains of HD patients. Observations here provide a structural basis for the alterations in cerebral white matter structure widely reported in HD patients. Collectively, our data demonstrate a dying-back pattern of degeneration for cortical projection neurons affected in HD, suggesting that axons represent an early and potentially critical target for mhtt toxicity. PMID:26123489

  4. Statistical Voxel-Based Methods and [18F]FDG PET Brain Imaging: Frontiers for the Diagnosis of AD.

    PubMed

    Gallivanone, Francesca; Della Rosa, Pasquale Anthony; Castiglioni, Isabella

    2016-01-01

    Recommended guidelines for the diagnosis of dementia due to Alzheimer's Disease (AD) were revised in recent years, including Positron Emission Tomography (PET) as an in-vivo diagnostic imaging technique for the diagnosis of neurodegeneration. In particular PET, using 18Ffluorodeoxiglucouse ([18F]FDG), is able to detect very early changes of glucose consumption at the synaptic level, enabling to support both early and differential diagnosis of AD. In standard clinical practice, interpretation of [18F] FDG-PET images is usually achieved through qualitative assessment. Visual inspection although only reveals information visible at human eyes resolution, while information at a higher resolution is missed. Furthermore, qualitative assessment depends on the degree of expertise of the clinician, preventing from the definition of accurate and standardized imaging biomarkers. Automated and computerized image processing methods have been proposed to support the in-vivo assessment of brain PET studies. In particular, objective statistical image analyses, enabling the comparison of one patient's images to a group of control images have been shown to carry important advantages for detecting significant metabolic changes, including the availability of more objective, cross-center reliable metrics and the detectability of brain subtle functional changes, as occurring in prodromal AD. The purpose of the current review is to provide a systematic overview encompassing the frontiers recently reached by quantitative approaches for the statistical analysis of PET brain images in the study of AD, with a particular focus on Statistical Parametric Mapping. Main achievements, e.g. in terms of standardized biomarkers of AD as well as of sensitivity and specificity, will be discussed. PMID:26567733

  5. [Post-mortem microbiology analysis].

    PubMed

    Fernández-Rodríguez, Amparo; Alberola, Juan; Cohen, Marta Cecilia

    2013-12-01

    Post-mortem microbiology is useful in both clinical and forensic autopsies, and allows a suspected infection to be confirmed. Indeed, it is routinely applied to donor studies in the clinical setting, as well as in sudden and unexpected death in the forensic field. Implementation of specific sampling techniques in autopsy can minimize the possibility of contamination, making interpretation of the results easier. Specific interpretation criteria for post-mortem cultures, the use of molecular diagnosis, and its fusion with molecular biology and histopathology have led to post-mortem microbiology playing a major role in autopsy. Multidisciplinary work involving microbiologists, pathologists, and forensic physicians will help to improve the achievements of post-mortem microbiology, prevent infectious diseases, and contribute to a healthier population. PMID:23195835

  6. Adding fuel to the fire: the impact of stress on the ageing brain.

    PubMed

    Prenderville, Jack A; Kennedy, Paul J; Dinan, Timothy G; Cryan, John F

    2015-01-01

    Both ageing and chronic stress are associated with altered brain plasticity, dysregulation of the immune system, and an increased risk of developing brain disorders; all of which have consequences for cognitive and emotional processing. Here we examine the similarities between behavioural changes during ageing and stress altered behaviours (anxiety, depressive-like behaviour, cognition, and sociability) in rodents and humans. The molecular mechanisms hypothesised to mediate age-related changes in brain function including dysfunction of the hypothalamic–pituitary–adrenal (HPA) axis, dysregulation of neurotransmission and neurotrophic factor signalling, increased inflammatory state, genetic and epigenetic changes, oxidative stress, metabolic changes, and changes in the microbiota–gut–brain axis are discussed. Finally, we explore how the already stressed aged brain psychologically and physiologically responds to external stressors. PMID:25705750

  7. A possible pathophysiological role of tyrosine hydroxylase in Parkinson's disease suggested by postmortem brain biochemistry: a contribution for the special 70th birthday symposium in honor of Prof. Peter Riederer.

    PubMed

    Nakashima, Akira; Ota, Akira; Kaneko, Yoko S; Mori, Keiji; Nagasaki, Hiroshi; Nagatsu, Toshiharu

    2013-01-01

    Postmortem brain biochemistry has revealed that the main symptom of movement disorder in Parkinson's disease (PD) is caused by a deficiency in dopamine (DA) at the nerve terminals of degenerating nigro-striatal DA neurons in the striatum. Since tyrosine hydroxylase (TH) is the rate-limiting enzyme for the biosynthesis of DA, TH may play an important role in the disease process of PD. DA regulated by TH activity is thought to interact with α-synuclein protein, which results in intracellular aggregates called Lewy bodies and causes apoptotic cell death during the aging process. Human TH has several isoforms produced by alternative mRNA splicing, which may affect activation by phosphorylation of serine residues in the N-terminus of TH. The activity and protein level of TH are decreased to cause DA deficiency in the striatum in PD. However, the homo-specific activity (activity/enzyme protein) of TH is increased. This increase in TH homo-specific activity suggests activation by increased phosphorylation at the N-terminus of the TH protein for a compensatory increase in DA synthesis. We recently found that phosphorylation of the N-terminal portion of TH triggers proteasomal degradation of the enzyme to increase TH turnover. We propose a hypothesis that this compensatory activation of TH by phosphorylation in the remaining DA neurons may contribute to a further decrease in TH protein and activity in DA neurons in PD, causing a vicious circle of decreasing TH activity, protein level and DA contents. Furthermore, increased TH homo-specific activity leading to an increase in DA may cause toxic reactive oxygen species in the neurons to promote neurodegeneration. PMID:22644539

  8. Metabolomics of Neurotransmitters and Related Metabolites in Post-Mortem Tissue from the Dorsal and Ventral Striatum of Alcoholic Human Brain.

    PubMed

    Kashem, Mohammed Abul; Ahmed, Selina; Sultana, Nilufa; Ahmed, Eakhlas U; Pickford, Russell; Rae, Caroline; Šerý, Omar; McGregor, Iain S; Balcar, Vladimir J

    2016-02-01

    We report on changes in neurotransmitter metabolome and protein expression in the striatum of humans exposed to heavy long-term consumption of alcohol. Extracts from post mortem striatal tissue (dorsal striatum; DS comprising caudate nucleus; CN and putamen; P and ventral striatum; VS constituted by nucleus accumbens; NAc) were analysed by high performance liquid chromatography coupled with tandem mass spectrometry. Proteomics was studied in CN by two-dimensional gel electrophoresis followed by mass-spectrometry. Proteomics identified 25 unique molecules expressed differently by the alcohol-affected tissue. Two were dopamine-related proteins and one a GABA-synthesizing enzyme GAD65. Two proteins that are related to apoptosis and/or neuronal loss (BiD and amyloid-β A4 precursor protein-binding family B member 3) were increased. There were no differences in the levels of dopamine (DA), 3,4-dihydrophenylacetic acid (DOPAC), serotonin (5HT), homovanillic acid (HVA), 5-hydroxyindoleacetic acid (HIAA), histamine, L-glutamate (Glu), γ-aminobutyric acid (GABA), tyrosine (Tyr) and tryptophan (Tryp) between the DS (CN and P) and VS (NAc) in control brains. Choline (Ch) and acetylcholine (Ach) were higher and norepinephrine (NE) lower, in the VS. Alcoholic striata had lower levels of neurotransmitters except for Glu (30 % higher in the alcoholic ventral striatum). Ratios of DOPAC/DA and HIAA/5HT were higher in alcoholic striatum indicating an increase in the DA and 5HT turnover. Glutathione was significantly reduced in all three regions of alcohol-affected striatum. We conclude that neurotransmitter systems in both the DS (CN and P) and the VS (NAc) were significantly influenced by long-term heavy alcohol intake associated with alcoholism . PMID:26801172

  9. Ad cerebrum per scientia: Ira Hirsh, psychoacoustics, and new approaches to understanding the human brain

    NASA Astrophysics Data System (ADS)

    Lauter, Judith

    2002-05-01

    As Research Director of CID, Ira emphasized the importance of combining information from biology with rigorous studies of behavior, such as psychophysics, to better understand how the brain and body accomplish the goals of everyday life. In line with this philosophy, my doctoral dissertation sought to explain brain functional asymmetries (studied with dichotic listening) in terms of the physical dimensions of a library of test sounds designed to represent a speech-music continuum. Results highlighted individual differences plus similarities in terms of patterns of relative ear advantages, suggesting an organizational basis for brain asymmetries depending on physical dimensions of stimulus and gesture with analogs in auditory, visual, somatosensory, and motor systems. My subsequent work has employed a number of noninvasive methods (OAEs, EPs, qEEG, PET, MRI) to explore the neurobiological bases of individual differences in general and functional asymmetries in particular. This research has led to (1) the AXS test battery for assessing the neurobiology of human sensory-motor function; (2) the handshaking model of brain function, describing dynamic relations along all three body/brain axes; (3) the four-domain EPIC model of functional asymmetries; and (4) the trimodal brain, a new model of individual differences based on psychoimmunoneuroendocrinology.

  10. Adenosine A1( )receptors are selectively coupled to Gα(i-3) in postmortem human brain cortex: Guanosine-5'-O-(3-[(35)S]thio)triphosphate ([(35)S]GTPγS) binding/immunoprecipitation study.

    PubMed

    Odagaki, Yuji; Kinoshita, Masakazu; Ota, Toshio; Meana, J Javier; Callado, Luis F; García-Sevilla, Jesús A

    2015-10-01

    By means of guanosine-5'-O-(3-[(35)S]thio)triphosphate ([(35)S]GTPγS) binding assay combined with immunoprecipitation using anti-Gα subunit antibody, we recently reported 5-HT2A receptor- and M1 muscarinic acetylcholine receptor-mediated Gαq activation in rat cerebral cortical membranes (Odagaki et al., 2014). In the present study, this method has been applied to postmortem human brains, with focusing on adenosine receptor-mediated G-protein activation. In the exploratory experiments using a series of agonists and the antibodies specific to each Gα subtypes in the presence of low (10 nM) or high (50 μM) concentration of GDP, the most prominent increases in specific [(35)S]GTPγS binding in the membranes prepared from human prefrontal cortex were obtained for the combinations of adenosine (1mM)/anti-Gαi-3 in the presence of 50 μM GDP as well as 5-HT (100 μM)/anti-Gαq and carbachol (1mM)/anti-Gαq in the presence of 10nM GDP. Adenosine-induced activation of Gαi-3 emerged only when GDP concentrations were increased higher than 10 μM, and the following experiments were performed in the presence of 300 μM GDP. Adenosine increased specific [(35)S]GTPγS binding to Gαi-3 in a concentration-dependent manner to 251.4% of the basal unstimulated binding, with an EC50 of 1.77 μM. The involvement of adenosine A1 receptor was verified by the experiments using selective agonists and antagonists at adenosine A1 or A3 receptor. Among the α subunits of Gi/o class (Gαi-1, Gαi-2, Gαi-3, and Gαo.), only Gαi-3 was activated by 1mM adenosine, indicating that human brain adenosine A1 receptor is coupled preferentially, if not exclusively, to Gαi-3. PMID:26213104

  11. Post-mortem clinical pharmacology

    PubMed Central

    Ferner, R E

    2008-01-01

    Clinical pharmacology assumes that deductions can be made about the concentrations of drugs from a knowledge of the pharmacokinetic parameters in an individual; and that the effects are related to the measured concentration. Post-mortem changes render the assumptions of clinical pharmacology largely invalid, and make the interpretation of concentrations measured in post-mortem samples difficult or impossible. Qualitative tests can show the presence of substances that were not present in life, and can fail to detect substances that led to death. Quantitative analysis is subject to error in itself, and because post-mortem concentrations vary in largely unpredictable ways with the site and time of sampling, as a result of the phenomenon of post-mortem redistribution. Consequently, compilations of ‘lethal concentrations’ are misleading. There is a lack of adequate studies of the true relationship between fatal events and the concentrations that can be measured subsequently, but without such studies, clinical pharmacologists and others should be wary of interpreting post-mortem measurements. PMID:18637886

  12. Adding Words to the Brain's Visual Dictionary: Novel Word Learning Selectively Sharpens Orthographic Representations in the VWFA

    PubMed Central

    Glezer, Laurie S.; Kim, Judy; Rule, Josh; Jiang, Xiong

    2015-01-01

    The nature of orthographic representations in the human brain is still subject of much debate. Recent reports have claimed that the visual word form area (VWFA) in left occipitotemporal cortex contains an orthographic lexicon based on neuronal representations highly selective for individual written real words (RWs). This theory predicts that learning novel words should selectively increase neural specificity for these words in the VWFA. We trained subjects to recognize novel pseudowords (PWs) and used fMRI rapid adaptation to compare neural selectivity with RWs, untrained PWs (UTPWs), and trained PWs (TPWs). Before training, PWs elicited broadly tuned responses, whereas responses to RWs indicated tight tuning. After training, TPW responses resembled those of RWs, whereas UTPWs continued to show broad tuning. This change in selectivity was specific to the VWFA. Therefore, word learning appears to selectively increase neuronal specificity for the new words in the VWFA, thereby adding these words to the brain's visual dictionary. PMID:25810526

  13. Rapid alteration of protein phosphorylation during postmortem: implication in the study of protein phosphorylation.

    PubMed

    Wang, Yifan; Zhang, Yanchong; Hu, Wen; Xie, Shutao; Gong, Cheng-Xin; Iqbal, Khalid; Liu, Fei

    2015-01-01

    Protein phosphorylation is an important post-translational modification of proteins. Postmortem tissues are widely being utilized in the biomedical studies, but the effects of postmortem on protein phosphorylation have not been received enough attention. In the present study, we found here that most proteins in mouse brain, heart, liver, and kidney were rapidly dephosphorylated to various degrees during 20 sec to 10 min postmortem. Phosphorylation of tau at Thr212 and glycogen synthase kinase 3β (GSK-3β) at Ser9 was reduced by 50% in the brain with 40 sec postmortem, a regular time for tissue processing. During postmortem, phosphorylation of cAMP-dependent protein kinase (PKA) and AMP activated kinase (AMPK) was increased in the brain, but not in other organs. Perfusion of the brain with cold or room temperature phosphate-buffered saline (PBS) also caused significant alteration of protein phosphorylation. Cooling down and maintaining mouse brains in the ice-cold buffer prevented the alteration effectively. This study suggests that phosphorylation of proteins is rapidly changed during postmortem. Thus, immediate processing of tissues followed by cooling down in ice-cold buffer is vitally important and perfusion has to be avoided when protein phosphorylation is to be studied. PMID:26511732

  14. Rapid alteration of protein phosphorylation during postmortem: implication in the study of protein phosphorylation

    PubMed Central

    Wang, Yifan; Zhang, Yanchong; Hu, Wen; Xie, Shutao; Gong, Cheng-Xin; Iqbal, Khalid; Liu, Fei

    2015-01-01

    Protein phosphorylation is an important post-translational modification of proteins. Postmortem tissues are widely being utilized in the biomedical studies, but the effects of postmortem on protein phosphorylation have not been received enough attention. In the present study, we found here that most proteins in mouse brain, heart, liver, and kidney were rapidly dephosphorylated to various degrees during 20 sec to 10 min postmortem. Phosphorylation of tau at Thr212 and glycogen synthase kinase 3β (GSK-3β) at Ser9 was reduced by 50% in the brain with 40 sec postmortem, a regular time for tissue processing. During postmortem, phosphorylation of cAMP-dependent protein kinase (PKA) and AMP activated kinase (AMPK) was increased in the brain, but not in other organs. Perfusion of the brain with cold or room temperature phosphate-buffered saline (PBS) also caused significant alteration of protein phosphorylation. Cooling down and maintaining mouse brains in the ice-cold buffer prevented the alteration effectively. This study suggests that phosphorylation of proteins is rapidly changed during postmortem. Thus, immediate processing of tissues followed by cooling down in ice-cold buffer is vitally important and perfusion has to be avoided when protein phosphorylation is to be studied. PMID:26511732

  15. Adding chemo after radiation treatment improves survival for adults with a type of brain tumor

    Cancer.gov

    Adults with low-grade gliomas, a form of brain tumor, who received chemotherapy following completion of radiation therapy lived longer than patients who received radiation therapy alone, according to long-term follow-up results from a NIH-supported random

  16. Postmortem angiography using femoral cannulation and postmortem microbiology.

    PubMed

    Palmiere, Cristian; Egger, Coraline; Grabherr, Silke; Jaton-Ogay, Katia; Greub, Gilbert

    2015-07-01

    Despite the undeniable advantages of postmortem angiography, numerous questions have arisen concerning the influence that the injected contrast media may exercise on biological fluids and tissues collected for toxicological and biochemical investigations. Moreover, cardiac blood for microbiological investigations cannot be obtained post-angiography. In this study, we examined whether the peripheral blood collected prior to postmortem angiography, using percutaneous access to femoral vessels after skin surface disinfection, could be suitable for microbiological investigations when postmortem angiography with femoral vessel cannulation is also performed. A total of 66 cases were included in the study and were divided into two subgroups (angiography and bacteriology group, 33 cases and control group, 33 cases). Autopsies, histology, toxicology, bacteriology, and biochemical investigations (procalcitonin, C-reactive protein, interleukin-6, and soluble triggering receptors expressed on myeloid cells type 1) were performed in all cases. No statistically significant differences between the two groups were noted, and identified category distribution (death unrelated to infection, true infection, false positive, and undetermined) was rather similar in both studied populations. These preliminary results suggest that postmortem angiography using a femoral approach does not constitute an impediment to the collection of peripheral blood for microbiology and vice versa. Moreover, the use of femoral blood for microbiology does not lead to an increased risk of doubtful results. PMID:25381195

  17. Radiolabled Polymeric Nanoparticles for Imaging Alzheimer's Plaques in a Mouse Model of Alzheimer's Disease (AD)

    NASA Astrophysics Data System (ADS)

    Kulkarni, P. V.; Roney, C. R.; Arora, V.; Bennett, M.; Antich, P. P.; Bonte, F. J.

    2009-03-01

    We have shown that, clioquinol (CQ) (5-chloro-7-iodo-8 hydroxy quinoline) can be radioiodinated and has rapid brain uptake and fast clearance from the blood and brain in normal mice. In order to enhance its brain uptake and retard the fast brain clearance, we incorporated it into butylpolycyanoacrylate (BCA) nanoparticles (NP). Selective localization of 125I CQ BCA nanoparticles was observed in autoradiograph of Alzheimer's Disease (AD) patient's postmortem brain sections. We studied its biodistribution in normal mice and experimental AD mice. AD lesions were created by administration of preformed aggregates of A-beta peptide (A□42) into hippocampus of mice using a stereotactic device. Biodistribution and ex-vivo autoradiography of the brains of mice injected with 125I CQ BCA nanoparticles showed that: 1. nanoparticles enhanced (1.5-2 times) the brain delivery of the 125I-CQ 2. Autoradiograph of AD brain sections showed localized uptake of the radiotracer and 3. experimental animal brains had positive autoradiogram compared to the control animals and animals injected with the free drug. Our data indicate that butyl polycyanoacrylate nanoparticles may be useful drug delivery vehicles for imaging AD with amyloid specific dyes.

  18. Setting up a postmortem service.

    PubMed

    der Burgt, Guda van

    2016-06-25

    Pets and pony camp, and a wish for a career that involved working with her hands, led Guda van der Burgt to study veterinary medicine at Utrecht. Starting her working life with a cattle breeding company, she moved into large animal work, industry and state veterinary medicine, all of which gave her the skills to set up a postmortem examination service. PMID:27339933

  19. In vitro determination of normal and neoplastic human brain tissue optical properties using inverse adding-doubling.

    PubMed

    Gebhart, S C; Lin, W C; Mahadevan-Jansen, A

    2006-04-21

    To complement a project towards the development of real-time optical biopsy for brain tissue discrimination and surgical resection guidance, the optical properties of various brain tissues were measured in vitro and correlated to features within clinical diffuse reflectance tissue spectra measured in vivo. Reflectance and transmission spectra of in vitro brain tissue samples were measured with a single-integrating-sphere spectrometer for wavelengths 400-1300 nm and converted to absorption and reduced scattering spectra using an inverse adding-doubling technique. Optical property spectra were classified as deriving from white matter, grey matter or glioma tissue according to histopathologic diagnosis, and mean absorption and reduced scattering spectra were calculated for the three tissue categories. Absolute reduced scattering and absorption values and their relative differences between histopathological groups agreed with previously reported results with the exception that absorption coefficients were often overestimated, most likely due to biologic variability or unaccounted light loss during reflectance/transmission measurement. Absorption spectra for the three tissue classes were dominated by haemoglobin absorption below 600 nm and water absorption above 900 nm and generally determined the shape of corresponding clinical diffuse reflectance spectra. Reduced scattering spectral shapes followed the power curve predicted by the Rayleigh limit of Mie scattering theory. While tissue absorption governed the shape of clinical diffuse reflectance spectra, reduced scattering determined their relative emission intensities between the three tissue categories. PMID:16585842

  20. [Methodics and aspects of postmortem forensic psychiatric expertise in a civil law suit].

    PubMed

    Ileĭko, V R

    2002-01-01

    With the purpose of studying issues concerning conducting a postmortem forensic psychiatric examination (FPE) in a lawsuit, getting an expert opinion, an analysis was performed of 55 cases of postmortem FPE with respect to those subjects with mental disturbances secondary to vascular affection of the brain (cerebral atherosclerosis and relevant complications), having been within the competence of experts. Measures are submitted designed to do away with the disadvantages spotted. PMID:12587300

  1. Altered neuronal gene expression in brain regions differentially affected by Alzheimer’s disease: a reference data set

    PubMed Central

    Liang, Winnie S.; Dunckley, Travis; Beach, Thomas G.; Grover, Andrew; Mastroeni, Diego; Ramsey, Keri; Caselli, Richard J.; Kukull, Walter A.; McKeel, Daniel; Morris, John C.; Hulette, Christine M.; Schmechel, Donald; Reiman, Eric M.; Rogers, Joseph; Stephan, Dietrich A.

    2009-01-01

    Alzheimer’s Disease (AD) is the most widespread form of dementia during the later stages of life. If improved therapeutics are not developed, the prevalence of AD will drastically increase in the coming years as the world’s population ages. By identifying differences in neuronal gene expression profiles between healthy elderly persons and individuals diagnosed with AD, we may be able to better understand the molecular mechanisms that drive AD pathogenesis, including the formation of amyloid plaques and neurofibrillary tangles. In this study, we expression profiled histopathologically normal cortical neurons collected with laser capture microdissection (LCM) from six anatomically and functionally discrete postmortem brain regions in 34 AD-afflicted individuals, using Affymetrix Human Genome U133 Plus 2.0 microarrays. These regions include the entorhinal cortex, hippocampus, middle temporal gyrus, posterior cingulate cortex, superior frontal gyrus, and primary visual cortex. This study is predicated on previous parallel research on the postmortem brains of the same six regions in 14 healthy elderly individuals, for which LCM neurons were similarly processed for expression analysis. We identified significant regional differential expression in AD brains compared with control brains including expression changes of genes previously implicated in AD pathogenesis, particularly with regards to tangle and plaque formation. Pinpointing the expression of factors that may play a role in AD pathogenesis provides a foundation for future identification of new targets for improved AD therapeutics. We provide this carefully phenotyped, laser capture microdissected intraindividual brain region expression data set to the community as a public resource. PMID:18270320

  2. Gabapentin concentrations and postmortem distribution.

    PubMed

    Hamm, Catherine E; Gary, Ray D; McIntyre, Iain M

    2016-05-01

    Gabapentin is a widely prescribed medication used primarily for the treatment of epilepsy and neuropathic pain. Gabapentin has a favorable adverse effect profile in therapeutic dosing with the most common reported effects being dizziness, fatigue, drowsiness, weight gain, and peripheral edema. Even with intentional self-poisonings, serious effects are generally rare. In this report, gabapentin analyses were performed on 30 postmortem cases that had peripheral blood, central blood and liver tissue. Overall the central to peripheral blood (C/P) ratio mean was 0.90±0.24 (mean±standard deviation), and a median of 0.97. The liver to peripheral blood (L/P) ratio mean was 0.68±0.26L/kg (mean±standard deviation), and a median of 0.65L/kg. An additional case, where both antemortem blood and postmortem peripheral blood specimens were available, revealed the same gabapentin concentration in both specimens. Taken together, the data presented suggests that gabapentin is unlikely to show postmortem redistribution. PMID:27038659

  3. Enhanced taupathy and AD-like pathology in aged primate brains decades after infantile exposure to Lead (Pb)

    PubMed Central

    Bihaqi, Syed Waseem; Zawia, Nasser H

    2013-01-01

    Late Onset Alzheimer Disease (LOAD) constitutes the majority of AD cases (~90%). Amyloidosis and tau pathology, which are present in AD brains, appear to be sporadic in nature. We have previously shown that infantile lead (Pb) exposure is associated with a change in the expression and regulation of the amyloid precursor protein (APP) and its beta amyloid (Aβ) products in old age. Here we report that infantile Pb exposure elevated the mRNA and protein levels of tau as well as its transcriptional regulators namely specificity protein 1 and 3 (Sp1 and Sp3) in aged primates. These changes were also accompanied by an enhancement in site-specific tau phosphorylation as well as an increase in the mRNA and protein levels of cyclin dependent kinase 5 (cdk5). There was also a change in the protein ratio of p35/p25 with more Serine/Threonine phosphatase activity present in aged primates exposed to Pb as infants. These molecular alterations favored abundant tau phosphorylation and immunoreactivity in the frontal cortex of aged primates with prior Pb exposure. These findings provide more evidence that neurodegenerative diseases may be products of environmental influences that occur during the development. PMID:23973560

  4. Streptozotocin Intracerebroventricular-Induced Neurotoxicity and Brain Insulin Resistance: a Therapeutic Intervention for Treatment of Sporadic Alzheimer's Disease (sAD)-Like Pathology.

    PubMed

    Kamat, Pradip K; Kalani, Anuradha; Rai, Shivika; Tota, Santosh Kumar; Kumar, Ashok; Ahmad, Abdullah S

    2016-09-01

    Alzheimer's disease (AD) is a neurodegenerative disorder that is remarkably characterized by pathological hallmarks which include amyloid plaques, neurofibrillary tangles, neuronal loss, and progressive cognitive loss. Several well-known genetic mutations which are being used for the development of a transgenic model of AD lead to an early onset familial AD (fAD)-like condition. However, these settings are only reasons for a small percentage of the total AD cases. The large majorities of AD cases are considered as a sporadic in origin and are less influenced by a single mutation of a gene. The etiology of sporadic Alzheimer's disease (sAD) remains unclear, but numerous risk factors have been identified that increase the chance of developing AD. Among these risk factors are insulin desensitization/resistance state, oxidative stress, neuroinflammation, synapse dysfunction, tau hyperphosphorylation, and deposition of Aβ in the brain. Subsequently, these risk factors lead to development of sAD. However, the underlying molecular mechanism is not so clear. Streptozotocin (STZ) produces similar characteristic pathology of sAD such as altered glucose metabolism, insulin signaling, synaptic dysfunction, protein kinases such as protein kinase B/C, glycogen synthase-3β (GSK-3β) activation, tau hyperphosphorylation, Aβ deposition, and neuronal apoptosis. Further, STZ also leads to inhibition of Akt/PKB, insulin receptor (IR) signaling molecule, and insulin resistance in brain. These alterations mediated by STZ can be used to explore the underlying molecular and pathophysiological mechanism of AD (especially sAD) and their therapeutic intervention for drug development against AD pathology. PMID:26298663

  5. Bridging the gap between MRI and postmortem research in autism.

    PubMed

    Schumann, Cynthia Mills; Nordahl, Christine Wu

    2011-03-22

    Autism is clearly a disorder of neural development, but when, where, and how brain pathology occurs remain elusive. Typical brain development is comprised of several stages, including proliferation and migration of neurons, creation of dendritic arbors and synaptic connections, and eventually dendritic pruning and programmed cell death. Any deviation at one or more of these stages could produce catastrophic downstream effects. MRI studies of autism have provided important clues, describing an aberrant trajectory of growth during early childhood that is both present in the whole brain and marked in specific structures such as the amygdala. However, given the coarse resolution of MRI, the field must also look towards postmortem human brain research to help elucidate the neurobiological underpinnings of MRI volumetric findings. Likewise, studies of postmortem tissue may benefit by looking to the findings from MRI studies to narrow hypotheses and target specific brain regions and subject populations. In this review, we discuss the strengths, limitations, and major contributions of each approach to autism research. We then describe how they relate and what they can learn from each other. Only by integrating these approaches will we be able to fully explain the neuropathology of autism. PMID:20869352

  6. Bridging the Gap between MRI and Postmortem Research in Autism

    PubMed Central

    Schumann, Cynthia Mills; Nordahl, Christine Wu

    2010-01-01

    Autism is clearly a disorder of neural development, but when, where, and how brain pathology occurs remains elusive. Typical brain development is comprised of several stages, including the proliferation and migration of neurons, creation of dendritic arbors and synaptic connections, and eventually dendritic pruning and programmed cell death. Any deviation at one or more of these stages could produce catastrophic downstream effects. MRI studies of autism have provided important clues, describing an aberrant trajectory of growth during early childhood that is both present in total brain and marked in specific structures such as the amygdala. However, given the coarse resolution of MRI, the field must also look towards postmortem human brain research to help elucidate the neurobiological underpinnings of MRI volumetric findings. Likewise, studies of postmortem tissue may benefit by looking to findings from MRI studies to narrow hypotheses and target specific brain regions. In this review, we discuss the strengths, limitations, and major contributions of each approach to autism research. We then describe how they relate and what they can learn from each other. Only by integrating these approaches will we be able to fully explain the neuropathology of autism. PMID:20869352

  7. Lactotransferrin immunocytochemistry in Alzheimer and normal human brain.

    PubMed Central

    Kawamata, T.; Tooyama, I.; Yamada, T.; Walker, D. G.; McGeer, P. L.

    1993-01-01

    Lactotransferrin (LF) expression was investigated immunocytochemically in postmortem brain tissues of normal controls and patients with Alzheimer's disease (AD). The antibody to LF stained some neurons weakly in young adult brains, but it stained many neurons as well as the glia of all types in elderly brains. LF expression was greatly up-regulated in both neurons and glia in affected AD tissue. It was very strongly associated with such extracellular pathological entities as diffuse and consolidated amyloid deposits and extracellular neurofibrillary tangles. In addition, it was identified in a minority of intracellular neurofibrillary tangles, neuropil threads, and degenerative neurites. LF is an iron scavenger and a complement inhibitor. Up-regulation may be a defense mechanism in AD-affected brain tissue. Images Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 PMID:8494052

  8. Preclinical Properties of 18F-AV-45: A PET Agent for Aβ Plaques in the Brain

    PubMed Central

    Choi, Seok Rye; Golding, Geoff; Zhuang, Zhiping; Zhang, Wei; Lim, Nathaniel; Hefti, Franz; Benedum, Tyler E.; Kilbourn, Michael R.; Skovronsky, Daniel; Kung, Hank F.

    2011-01-01

    β-amyloid plaques (Aβ plaques) in the brain, containing predominantly fibrillary Aβ peptide aggregates, represent a defining pathologic feature of Alzheimer disease (AD). Imaging agents targeting the Aβ plaques in the living human brain are potentially valuable as biomarkers of pathogenesis processes in AD. (E)-4-(2-(6-(2-(2-(2-18F-fluoroethoxy)ethoxy)ethoxy)pyridin-3-yl)vinyl)-N-methyl benzenamine (18F-AV-45) is such as an agent currently in phase III clinical studies for PET of Aβ plaques in the brain. Methods In vitro binding of 18F-AV-45 to Aβ plaques in the postmortem AD brain tissue was evaluated by in vitro binding assay and autoradiography. In vivo biodistribution of 18F-AV-45 in mice and ex vivo autoradiography of AD transgenic mice (APPswe/PSEN1) with Aβ aggregates in the brain were performed. Small-animal PET of a monkey brain after an intravenous injection of 18F-AV-45 was evaluated. Results 18F-AV-45 displayed a high binding affinity and specificity to Aβ plaques (Kd, 3.72 ± 0.30 nM). In vitro autoradiography of postmortem human brain sections showed substantial plaque labeling in AD brains and not in the control brains. Initial high brain uptake and rapid washout from the brain of healthy mice and monkey were observed. Metabolites produced in the blood of healthy mice after an intravenous injection were identified. 18F-AV-45 displayed excellent binding affinity to Aβ plaques in the AD brain by ex vivo autoradiography in transgenic AD model mice. The results lend support that 18F-AV-45 may be a useful PET agent for detecting Aβ plaques in the living human brain. PMID:19837759

  9. Mitochondrial DNA Rearrangement Spectrum in Brain Tissue of Alzheimer’s Disease: Analysis of 13 Cases

    PubMed Central

    Chen, Yucai; Liu, Changsheng; Parker, William Davis; Chen, Hongyi; Beach, Thomas G.; Liu, Xinhua; Serrano, Geidy E.; Lu, Yanfen; Huang, Jianjun; Yang, Kunfang; Wang, Chunmei

    2016-01-01

    Background Mitochondrial dysfunction may play a central role in the pathologic process of Alzheimer’s disease (AD), but there is still a scarcity of data that directly links the pathology of AD with the alteration of mitochondrial DNA. This study aimed to provide a comprehensive assessment of mtDNA rearrangement events in AD brain tissue. Patients and Methods Postmortem frozen human brain cerebral cortex samples were obtained from the Banner Sun Health Research Institute Brain and Body Donation Program, Sun City, AZ. Mitochondria were isolated and direct sequence by using MiSeq®, and analyzed by relative software. Results Three types of mitochondrial DNA (mtDNA) rearrangements have been seen in post mortem human brain tissue from patients with AD and age matched control. These observed rearrangements include a deletion, F-type rearrangement, and R-type rearrangement. We detected a high level of mtDNA rearrangement in brain tissue from cognitively normal subjects, as well as the patients with Alzheimer's disease (AD). The rate of rearrangements was calculated by dividing the number of positive rearrangements by the coverage depth. The rearrangement rate was significantly higher in AD brain tissue than in control brain tissue (17.9%versus 6.7%; p = 0.0052). Of specific types of rearrangement, deletions were markedly increased in AD (9.2% versus 2.3%; p = 0.0005). Conclusions Our data showed that failure of mitochondrial DNA in AD brain might be important etiology of AD pathology. PMID:27299301

  10. Altered Expression of Diabetes-Related Genes in Alzheimer's Disease Brains: The Hisayama Study

    PubMed Central

    Hokama, Masaaki; Oka, Sugako; Leon, Julio; Ninomiya, Toshiharu; Honda, Hiroyuki; Sasaki, Kensuke; Iwaki, Toru; Ohara, Tomoyuki; Sasaki, Tomio; LaFerla, Frank M.; Kiyohara, Yutaka; Nakabeppu, Yusaku

    2014-01-01

    Diabetes mellitus (DM) is considered to be a risk factor for dementia including Alzheimer's disease (AD). However, the molecular mechanism underlying this risk is not well understood. We examined gene expression profiles in postmortem human brains donated for the Hisayama study. Three-way analysis of variance of microarray data from frontal cortex, temporal cortex, and hippocampus was performed with the presence/absence of AD and vascular dementia, and sex, as factors. Comparative analyses of expression changes in the brains of AD patients and a mouse model of AD were also performed. Relevant changes in gene expression identified by microarray analysis were validated by quantitative real-time reverse-transcription polymerase chain reaction and western blotting. The hippocampi of AD brains showed the most significant alteration in gene expression profile. Genes involved in noninsulin-dependent DM and obesity were significantly altered in both AD brains and the AD mouse model, as were genes related to psychiatric disorders and AD. The alterations in the expression profiles of DM-related genes in AD brains were independent of peripheral DM-related abnormalities. These results indicate that altered expression of genes related to DM in AD brains is a result of AD pathology, which may thereby be exacerbated by peripheral insulin resistance or DM. PMID:23595620

  11. Postmortem inflation and fixation of human lungs

    PubMed Central

    Wright, B. M.; Slavin, G.; Kreel, L.; Callan, K.; Sandin, Brenda

    1974-01-01

    Wright, B. M., Slavin, G., Kreel, L., Callan, K., and Sandin, Brenda (1974).Thorax, 29, 189-194. Postmortem inflation and fixation of human lungs. A method of fixing lungs by inflating them with heated formalin vapour is described. This method facilitates postmortem correlations between radiographic and histological appearances. Images PMID:4598582

  12. Graded perturbations of metabolism in multiple regions of human brain in Alzheimer's disease: Snapshot of a pervasive metabolic disorder

    PubMed Central

    Xu, Jingshu; Begley, Paul; Church, Stephanie J.; Patassini, Stefano; Hollywood, Katherine A.; Jüllig, Mia; Curtis, Maurice A.; Waldvogel, Henry J.; Faull, Richard L.M.; Unwin, Richard D.; Cooper, Garth J.S.

    2016-01-01

    Alzheimer's disease (AD) is an age-related neurodegenerative disorder that displays pathological characteristics including senile plaques and neurofibrillary tangles. Metabolic defects are also present in AD-brain: for example, signs of deficient cerebral glucose uptake may occur decades before onset of cognitive dysfunction and tissue damage. There have been few systematic studies of the metabolite content of AD human brain, possibly due to scarcity of high-quality brain tissue and/or lack of reliable experimental methodologies. Here we sought to: 1) elucidate the molecular basis of metabolic defects in human AD-brain; and 2) identify endogenous metabolites that might guide new approaches for therapeutic intervention, diagnosis or monitoring of AD. Brains were obtained from nine cases with confirmed clinical/neuropathological AD and nine controls matched for age, sex and post-mortem delay. Metabolite levels were measured in post-mortem tissue from seven regions: three that undergo severe neuronal damage (hippocampus, entorhinal cortex and middle-temporal gyrus); three less severely affected (cingulate gyrus, sensory cortex and motor cortex); and one (cerebellum) that is relatively spared. We report a total of 55 metabolites that were altered in at least one AD-brain region, with different regions showing alterations in between 16 and 33 metabolites. Overall, we detected prominent global alterations in metabolites from several pathways involved in glucose clearance/utilization, the urea cycle, and amino-acid metabolism. The finding that potentially toxigenic molecular perturbations are widespread throughout all brain regions including the cerebellum is consistent with a global brain disease process rather than a localized effect of AD on regional brain metabolism. PMID:26957286

  13. Graded perturbations of metabolism in multiple regions of human brain in Alzheimer's disease: Snapshot of a pervasive metabolic disorder.

    PubMed

    Xu, Jingshu; Begley, Paul; Church, Stephanie J; Patassini, Stefano; Hollywood, Katherine A; Jüllig, Mia; Curtis, Maurice A; Waldvogel, Henry J; Faull, Richard L M; Unwin, Richard D; Cooper, Garth J S

    2016-06-01

    Alzheimer's disease (AD) is an age-related neurodegenerative disorder that displays pathological characteristics including senile plaques and neurofibrillary tangles. Metabolic defects are also present in AD-brain: for example, signs of deficient cerebral glucose uptake may occur decades before onset of cognitive dysfunction and tissue damage. There have been few systematic studies of the metabolite content of AD human brain, possibly due to scarcity of high-quality brain tissue and/or lack of reliable experimental methodologies. Here we sought to: 1) elucidate the molecular basis of metabolic defects in human AD-brain; and 2) identify endogenous metabolites that might guide new approaches for therapeutic intervention, diagnosis or monitoring of AD. Brains were obtained from nine cases with confirmed clinical/neuropathological AD and nine controls matched for age, sex and post-mortem delay. Metabolite levels were measured in post-mortem tissue from seven regions: three that undergo severe neuronal damage (hippocampus, entorhinal cortex and middle-temporal gyrus); three less severely affected (cingulate gyrus, sensory cortex and motor cortex); and one (cerebellum) that is relatively spared. We report a total of 55 metabolites that were altered in at least one AD-brain region, with different regions showing alterations in between 16 and 33 metabolites. Overall, we detected prominent global alterations in metabolites from several pathways involved in glucose clearance/utilization, the urea cycle, and amino-acid metabolism. The finding that potentially toxigenic molecular perturbations are widespread throughout all brain regions including the cerebellum is consistent with a global brain disease process rather than a localized effect of AD on regional brain metabolism. PMID:26957286

  14. Exenatide promotes cognitive enhancement and positive brain metabolic changes in PS1-KI mice but has no effects in 3xTg-AD animals

    PubMed Central

    Bomba, M; Ciavardelli, D; Silvestri, E; Canzoniero, L MT; Lattanzio, R; Chiappini, P; Piantelli, M; Di Ilio, C; Consoli, A; Sensi, S L

    2013-01-01

    Recent studies have shown that type 2 diabetes mellitus (T2DM) is a risk factor for cognitive dysfunction or dementia. Insulin resistance is often associated with T2DM and can induce defective insulin signaling in the central nervous system as well as increase the risk of cognitive impairment in the elderly. Glucagone like peptide-1 (GLP-1) is an incretin hormone and, like GLP-1 analogs, stimulates insulin secretion and has been employed in the treatment of T2DM. GLP-1 and GLP-1 analogs also enhance synaptic plasticity and counteract cognitive deficits in mouse models of neuronal dysfunction and/or degeneration. In this study, we investigated the potential neuroprotective effects of long-term treatment with exenatide, a GLP-1 analog, in two animal models of neuronal dysfunction: the PS1-KI and 3xTg-AD mice. We found that exenatide promoted beneficial effects on short- and long-term memory performances in PS1-KI but not in 3xTg-AD animals. In PS1-KI mice, the drug increased brain lactate dehydrogenase activity leading to a net increase in lactate levels, while no effects were observed on mitochondrial respiration. On the contrary, exenatide had no effects on brain metabolism of 3xTg-AD mice. In summary, our data indicate that exenatide improves cognition in PS1-KI mice, an effect likely driven by increasing the brain anaerobic glycolysis rate. PMID:23640454

  15. Elevation of brain glucose and polyol-pathway intermediates with accompanying brain-copper deficiency in patients with Alzheimer's disease: metabolic basis for dementia.

    PubMed

    Xu, Jingshu; Begley, Paul; Church, Stephanie J; Patassini, Stefano; McHarg, Selina; Kureishy, Nina; Hollywood, Katherine A; Waldvogel, Henry J; Liu, Hong; Zhang, Shaoping; Lin, Wanchang; Herholz, Karl; Turner, Clinton; Synek, Beth J; Curtis, Maurice A; Rivers-Auty, Jack; Lawrence, Catherine B; Kellett, Katherine A B; Hooper, Nigel M; Vardy, Emma R L C; Wu, Donghai; Unwin, Richard D; Faull, Richard L M; Dowsey, Andrew W; Cooper, Garth J S

    2016-01-01

    Impairment of brain-glucose uptake and brain-copper regulation occurs in Alzheimer's disease (AD). Here we sought to further elucidate the processes that cause neurodegeneration in AD by measuring levels of metabolites and metals in brain regions that undergo different degrees of damage. We employed mass spectrometry (MS) to measure metabolites and metals in seven post-mortem brain regions of nine AD patients and nine controls, and plasma-glucose and plasma-copper levels in an ante-mortem case-control study. Glucose, sorbitol and fructose were markedly elevated in all AD brain regions, whereas copper was correspondingly deficient throughout (all P < 0.0001). In the ante-mortem case-control study, by contrast, plasma-glucose and plasma-copper levels did not differ between patients and controls. There were pervasive defects in regulation of glucose and copper in AD brain but no evidence for corresponding systemic abnormalities in plasma. Elevation of brain glucose and deficient brain copper potentially contribute to the pathogenesis of neurodegeneration in AD. PMID:27276998

  16. Elevation of brain glucose and polyol-pathway intermediates with accompanying brain-copper deficiency in patients with Alzheimer’s disease: metabolic basis for dementia

    PubMed Central

    Xu, Jingshu; Begley, Paul; Church, Stephanie J.; Patassini, Stefano; McHarg, Selina; Kureishy, Nina; Hollywood, Katherine A.; Waldvogel, Henry J.; Liu, Hong; Zhang, Shaoping; Lin, Wanchang; Herholz, Karl; Turner, Clinton; Synek, Beth J.; Curtis, Maurice A.; Rivers-Auty, Jack; Lawrence, Catherine B.; Kellett, Katherine A. B.; Hooper, Nigel M.; Vardy, Emma R. L. C.; Wu, Donghai; Unwin, Richard D.; Faull, Richard L. M.; Dowsey, Andrew W.; Cooper, Garth J. S.

    2016-01-01

    Impairment of brain-glucose uptake and brain-copper regulation occurs in Alzheimer’s disease (AD). Here we sought to further elucidate the processes that cause neurodegeneration in AD by measuring levels of metabolites and metals in brain regions that undergo different degrees of damage. We employed mass spectrometry (MS) to measure metabolites and metals in seven post-mortem brain regions of nine AD patients and nine controls, and plasma-glucose and plasma-copper levels in an ante-mortem case-control study. Glucose, sorbitol and fructose were markedly elevated in all AD brain regions, whereas copper was correspondingly deficient throughout (all P < 0.0001). In the ante-mortem case-control study, by contrast, plasma-glucose and plasma-copper levels did not differ between patients and controls. There were pervasive defects in regulation of glucose and copper in AD brain but no evidence for corresponding systemic abnormalities in plasma. Elevation of brain glucose and deficient brain copper potentially contribute to the pathogenesis of neurodegeneration in AD. PMID:27276998

  17. Postmortem imaging of sudden cardiac death.

    PubMed

    Michaud, Katarzyna; Grabherr, Silke; Jackowski, Christian; Bollmann, Marc Daniel; Doenz, Franceso; Mangin, Patrice

    2014-01-01

    Postmortem imaging is increasingly used in forensic practice in cases of natural deaths related to cardiovascular diseases, which represent the most common causes of death in developed countries. While radiological examination is generally considered to be a good complement for conventional autopsy, it was thought to have limited application in cardiovascular pathology. At present, multidetector computed tomography (MDCT), CT angiography, and cardiac magnetic resonance imaging (MRI) are used in postmortem radiological investigation of cardiovascular pathologies. This review presents the actual state of postmortem imaging for cardiovascular pathologies in cases of sudden cardiac death (SCD), taking into consideration both the advantages and limitations. The radiological evaluation of ischemic heart disease (IHD), the most frequent cause of SCD in the general population of industrialized countries, includes the examination of the coronary arteries and myocardium. Postmortem CT angiography (PMCTA) is very useful for the detection of stenoses and occlusions of coronary arteries but less so for the identification of ischemic myocardium. MRI is the method of choice for the radiological investigation of the myocardium in clinical practice, but its accessibility and application are still limited in postmortem practice. There are very few reports implicating postmortem radiology in the investigation of other causes of SCD, such as cardiomyopathies, coronary artery abnormalities, and valvular pathologies. Cardiomyopathies representing the most frequent cause of SCD in young athletes cannot be diagnosed by echocardiography, the most widely available technique in clinical practice for the functional evaluation of the heart and the detection of cardiomyopathies. PMCTA and MRI have the potential to detect advanced stages of diseases when morphological substrate is present, but these methods have yet to be sufficiently validated for postmortem cases. Genetically determined

  18. Postmortem calpain changes in ostrich skeletal muscle.

    PubMed

    Chang, Ya-Shiou; Hsu, Dun-Hui; Stromer, Mavin H; Chou, Rong-Ghi R

    2016-07-01

    The objective of this study was to study the postmortem calpain change in ostrich muscle. Iliotibialis cranialis and Obturatorius medialis muscles were removed from the both sides of carcasses (n=8). The muscles from the left side were sampled after 0, 1, 2, 3, and 7days of storage at 5°C, while the right-side muscles were taken at 1-, 3-, and 7-day postmortem for shear force measurements. The results showed that the calpain-1 activity was not detected in ostrich muscle during the entire 7-day postmortem storage period, while the calpain-11 was. The unautolyzed calpain-11 activity decreased and the autolyzed calpain-11 activity increased with time postmortem. Desmin content and shear force did not change during postmortem storage although a minor degradation of desmin was observed. Therefore, our results suggest that limited postmortem proteolysis (as suggested by the limited degradation of desmin) and tenderization might be due to the lack of calpain-1 and/or insufficient calpain-11 activity present in ostrich muscle. PMID:26971307

  19. [Post-mortem organ donation].

    PubMed

    Goroll, T; Gerresheim, G; Schaffartzik, W; Schwemmer, U

    2015-07-01

    In Germany approximately 3000 body organs are transplanted annually. In general, all artificially ventilated patients with diagnosed brain death are potential organ donors. All German hospitals are obliged to report potential organ donors and be actively involved in the organ donation process. These matters lie under the jurisdiction of the German transplantation act. An essential prerequisite for organ donation is the diagnosis of brain death according to the guidelines of the German Medical Association. Brain death is associated with complex pathophysiological changes in cardiopulmonary function as well as fluid, electrolyte and metabolic homeostasis. In the case of diagnosed brain death and with permission for organ donation, a precise organ-protective therapy is initiated, essentially focussing on optimal organ perfusion and oxygenation. The quality of organ protection has a direct influence on the outcome of transplantation. PMID:26174748

  20. Brain

    MedlinePlus

    ... will return after updating. Resources Archived Modules Updates Brain Cerebrum The cerebrum is the part of the ... the outside of the brain and spinal cord. Brain Stem The brain stem is the part of ...

  1. Hyperdensity of the Basilar Artery on Postmortem CT: A Potential Indicator for Basilar Artery Thrombosis.

    PubMed

    Garland, Jack; Tse, Rexson; Beh, Raymond J; Lyons, Timothy J; Cala, Allan D

    2016-06-01

    Basilar artery thrombosis constitutes 1% of all types of stroke, carries a mortality rate of up to 90%, and is one of the rarer causes of sudden death. It leads to brain stem ischemia and commonly presents with impaired consciousness, cranial nerve palsy, hemiplegia or quadriplegia, and sudden collapse. Clinically, the diagnosis of basilar artery thrombosis is made on clinical symptoms, along with a hyperdense basilar artery in antemortem computed tomography (CT) scan. To our knowledge, whether a hyperdense basilar artery indicates basilar artery thrombosis on postmortem CT scan is not documented in the literature. We present a case report of a 55-year-old man who on postmortem CT scan showed a hyperdense basilar artery and was subsequently confirmed to be a fatal basilar artery thrombosis. We suggest that a hyperdense basilar artery on postmortem CT should prompt the pathologist to consider basilar artery thrombosis. PMID:27049662

  2. Global and Site-Specific Changes in 5-Methylcytosine and 5-Hydroxymethylcytosine after Extended Post-mortem Interval

    PubMed Central

    Gross, Jeffrey A.; Nagy, Corina; Lin, Li; Bonneil, Éric; Maheu, Marissa; Thibault, Pierre; Mechawar, Naguib; Jin, Peng; Turecki, Gustavo

    2016-01-01

    There has been a growing interest in the study of epigenetic mechanisms to elucidate the molecular bases of human brain-related diseases and disorders. Frequently, researchers utilize post-mortem tissue with the assumption that post-mortem tissue decay has little or no effect on epigenetic marks. Although previous studies show no effect of post-mortem interval on certain epigenetic marks, no such research has been performed on cytosine modifications. In this study, we use DNA from the brains of adult Sprague Dawley rats subjected to post-mortem intervals at room temperature, ranging from 0 to 96 h, to assess the stability of cytosine modifications, namely 5-methycytosine and 5-hydroxymethylcytosine. Our results indicate that neither global nor site-specific levels of 5-methycytosine and 5-hydroxymethylcytosine are affected by the post-mortem intervals we studied. As such, the use of post-mortem tissue to study cytosine modifications in the context of neurological or neuropsychiatric disorders is appropriate. PMID:27446202

  3. Brain levels of sex steroid hormones in men and women during normal aging and in Alzheimer’s disease

    PubMed Central

    Rosario, Emily R.; Chang, Lilly; Head, Elizabeth H.; Stanczyk, Frank Z.; Pike, Christian J.

    2009-01-01

    We examined the relationships between normal aging, Alzheimer’s disease (AD), and brain levels of sex steroid hormones in men and women. In postmortem brain tissue from neuropathologically normal, postmenopausal women, we found no age-related changes in brain levels of either androgens or estrogens. In comparing women with and without AD at different ages, brain levels of estrogens and androgens were lower in AD cases aged 80 years and older but not significantly different in the 60–79 year age range. In male brains, we observed that normal aging was associated with significant decreases in androgens but not estrogens. Further, in men aged 60–79 years, brain levels of testosterone but not estrogens were lower in cases with mild neuropathological changes as well as those with advanced AD neuropathology. In male cases over age 80, brain levels hormones did not significantly vary by neuropathological status. To begin investigating the relationships between hormone levels and indices of AD neuropathology, we measured brain levels of soluble β-amyloid (Aβ). In male cases with mild neuropathological changes, we found an inverse relationship between brain levels of testosterone and soluble Aβ. Collectively, these findings demonstrate sex-specific relationships between normal, age-related depletion of androgens and estrogens in men and women, which may be relevant to development of AD. PMID:19428144

  4. Postmortem bacteriology: a re‐evaluation

    PubMed Central

    Morris, J A; Harrison, L M; Partridge, S M

    2006-01-01

    Aim To assess the value of postmortem bacteriology in necropsy practice, with specific emphasis on bacterial invasion of blood and cerebrospinal fluid (CSF). Methods A review of published articles on postmortem bacteriology. Studies were selected to cover the full range of necropsy practice including adults, the perinatal period, and infancy. The review covers over 5000 necropsies, mainly in adults, but including 1108 perinatal cases and 468 cases of sudden unexpected death in infancy. Data are available on 4992 blood cultures, 1168 specimens of CSF, and 743 cultures of spleen. Results Studies in which careful precautions have been taken to reduce contamination show that approximately two thirds of blood cultures are negative, two in nine yield a single isolate, and one in nine have a mixed growth. The postmortem interval has only a small effect on the isolation rate. A pure growth of a known pathogen has a more than 50% likelihood of being found in association with genuine infection in adults and in the perinatal period. Conclusions The main postmortem artefact is contamination, but this can be considerably reduced by careful technique. Agonal spread is less common than is often assumed. Postmortem translocation is not a problem if the body is appropriately stored. A pure growth of a pathogen in blood or CSF should be regarded as a possible contributing factor to death at all ages. PMID:16394274

  5. Postmortem perianal findings in children.

    PubMed

    McCann, J; Reay, D; Siebert, J; Stephens, B G; Wirtz, S

    1996-12-01

    The postmortem finding of anal dilation or an exposed pectinate line in children who have died under suspicious circumstances continues to raise the concern of possible sexual abuse. The following multicenter, collaborative study was designed to help address that question. Sixty-five subjects, ranging in age from birth to 17 years, were autopsied at three different sites. A standard protocol along with 35-mm cameras were used to record the results. Thirty-eight (58%) subjects were boys, and 27 (42%) were girls. Forty-two (65%) were white, 10 (15%) African-American, five (8%) Asian, three (5%) white Hispanic and five (8%) other. Fifty-seven (88%) were in Tanner stage I of secondary sexual development. Thirty-four (52%) died of natural causes, 26 (40%) from accidental injuries, three (5%) from other causes, and four (6%) as a result of a homicide. Forty-eight subjects (74%) had some dilation of the anal sphincters. In 21 children (32%), the entire anal canal, including the rectal ampulla, could be visualized. In another 21 (32%) subjects, the pectinate line was exposed. Only the outer portion of the anal canal opened in six children (10%), whereas 17 (26%) had no dilatation of the anus. Anal laxity led to flattened skin folds in 50 (77%), a shallow anal canal in 40 (62%), the exposure of both the pectinate line in 38 (59%), and the anal mucosa in 24 (37%). Venous congestion was present in 14 (22%), venous pooling in three (5%), erythema in six (9%), and increased pigmentation in eight (12%). Funneling was found in two (3%). Blood was present in three (5%), and an abrasion was discovered in one (2%). No fissures, lacerations, hemorrhoids, or scars were found in any of the children. Anal orifice size varied with the age of the child, the amount of traction applied to the buttocks, and a history of a CNS injury at the time of death. It is suggested, finally, that anal dilatation alone cannot be used a marker for prior sexual abuse and the exposure of the pectinate line

  6. ESPR postmortem imaging task force: where we begin.

    PubMed

    Arthurs, Owen J; van Rijn, Rick R; Whitby, Elspeth H; Johnson, Karl; Miller, Elka; Stenzel, Martin; Watt, Andrew; Taranath, Ajay; Perry, David H

    2016-08-01

    A new task force on postmortem imaging was established at the annual meeting of the European Society of Paediatric Radiology (ESPR) in Graz, Austria, in 2015. The postmortem task force is separate from the child abuse task force as it covers all aspects of fetal, neonatal and non-forensic postmortem imaging. The main focus of the task force is the guidance and standardization of non-radiographic postmortem imaging, particularly postmortem CT and postmortem MRI. This manuscript outlines the starting point of the task force, with a mission statement, outline of current experience, and short- and long-term goals. PMID:27412272

  7. Stereotactic radiosurgery as therapy for melanoma, renal carcinoma, and sarcoma brain metastases: Impact of added surgical resection and whole-brain radiotherapy

    SciTech Connect

    Rao, Ganesh; Klimo, Paul; Thompson, Clinton J.; Samlowski, Wolfram; Wang, Michael; Watson, Gordon; Shrieve, Dennis; Jensen, Randy L. . E-mail: randy.jensen@hsc.utah.edu

    2006-11-15

    Purpose: Brain metastases of melanoma, renal carcinoma, and sarcoma have traditionally responded poorly to conventional treatments, including surgery and whole-brain radiotherapy (WBRT). Several studies have suggested a beneficial effect of stereotactic radiosurgery (SRS). We evaluated our institutional experience with systematic SRS in patients harboring these 'radioresistant' metastases. Methods and Materials: A total of 68 patients with brain metastases from melanoma, renal carcinoma, and sarcoma underwent SRS with or without WBRT or surgical resection. All patients had Karnofsky performance scores >70, and SRS was performed before the initiation of systemic therapy. The survival time was calculated from the diagnosis of brain metastases using the Kaplan-Meier product-limit method. Statistical significance was calculated using the log-rank test. Factors influencing survival, including surgical resection, WBRT, gender, number of SRS sessions, and histologic type, were evaluated retrospectively using Cox univariate models. Results: The overall median survival was 427 days (14.2 months), which appears superior to the results obtained with conventional WBRT. The addition of neither surgery nor WBRT to SRS provided a statistically significant increase in survival. Conclusion: Our results suggest that patients undergoing SRS for up to five cerebral metastases from 'radioresistant' tumors (melanoma, renal cell carcinoma, and sarcoma) have survival rates comparable to those in other series of more selected patients. The addition of surgical resection or WBRT did not result in improved survival in our series.

  8. Increased brain uptake of targeted nanoparticles by adding an acid-cleavable linkage between transferrin and the nanoparticle core.

    PubMed

    Clark, Andrew J; Davis, Mark E

    2015-10-01

    Most therapeutic agents are excluded from entering the central nervous system by the blood-brain barrier (BBB). Receptor mediated transcytosis (RMT) is a common mechanism used by proteins, including transferrin (Tf), to traverse the BBB. Here, we prepared Tf-containing, 80-nm gold nanoparticles with an acid-cleavable linkage between the Tf and the nanoparticle core to facilitate nanoparticle RMT across the BBB. These nanoparticles are designed to bind to Tf receptors (TfRs) with high avidity on the blood side of the BBB, but separate from their multidentate Tf-TfR interactions upon acidification during the transcytosis process to allow release of the nanoparticle into the brain. These targeted nanoparticles show increased ability to cross an in vitro model of the BBB and, most important, enter the brain parenchyma of mice in greater amounts in vivo after systemic administration compared with similar high-avidity nanoparticles containing noncleavable Tf. In addition, we investigated this design with nanoparticles containing high-affinity antibodies (Abs) to TfR. With the Abs, the addition of the acid-cleavable linkage provided no improvement to in vivo brain uptake for Ab-containing nanoparticles, and overall brain uptake was decreased for all Ab-containing nanoparticles compared with Tf-containing ones. These results are consistent with recent reports of high-affinity anti-TfR Abs trafficking to the lysosome within BBB endothelium. In contrast, high-avidity, Tf-containing nanoparticles with the acid-cleavable linkage avoid major endothelium retention by shedding surface Tf during their transcytosis. PMID:26392563

  9. Frontiers for the Early Diagnosis of AD by Means of MRI Brain Imaging and Support Vector Machines.

    PubMed

    Salvatore, Christian; Battista, Petronilla; Castiglioni, Isabella

    2016-01-01

    The emergence of Alzheimer's Disease (AD) as a consequence of increasing aging population makes urgent the availability of methods for the early and accurate diagnosis. Magnetic Resonance Imaging (MRI) could be used as in vivo, non invasive tool to identify sensitive and specific markers of very early AD progression. In recent years, multivariate pattern analysis (MVPA) and machine- learning algorithms have attracted strong interest within the neuroimaging community, as they allow automatic classification of imaging data with higher performance than univariate statistical analysis. An exhaustive search of PubMed, Web of Science and Medline records was performed in this work, in order to retrieve studies focused on the potential role of MRI in aiding the clinician in early diagnosis of AD by using Support Vector Machines (SVMs) as MVPA automated classification method. A total of 30 studies emerged, published from 2008 to date. This review aims to give a state-of-the-art overview about SVM for the early and differential diagnosis of AD-related pathologies by means of MRI data, starting from preliminary steps such as image pre-processing, feature extraction and feature selection, and ending with classification, validation strategies and extraction of MRI-related biomarkers. The main advantages and drawbacks of the different techniques were explored. Results obtained by the reviewed studies were reported in terms of classification performance and biomarker outcomes, in order to shed light on the parameters that accompany normal and pathological aging. Unresolved issues and possible future directions were finally pointed out. PMID:26567735

  10. Generation of Bioactive Oxylipins from Exogenously Added Arachidonic, Eicosapentaenoic and Docosahexaenoic Acid in Primary Human Brain Microvessel Endothelial Cells.

    PubMed

    Aukema, Harold M; Winter, Tanja; Ravandi, Amir; Dalvi, Siddhartha; Miller, Donald W; Hatch, Grant M

    2016-05-01

    The human blood-brain barrier (BBB) is the restrictive barrier between the brain parenchyma and the circulating blood and is formed in part by microvessel endothelial cells. The brain contains significant amounts of arachidonic acid (ARA), and docosahexaenoic acid (DHA), which potentially give rise to the generation of bioactive oxylipins. Oxylipins are oxygenated fatty acid metabolites that are involved in an assortment of biological functions regulating neurological health and disease. Since it is not known which oxylipins are generated by human brain microvessel endothelial cells (HBMECs), they were incubated for up to 30 min in the absence or presence of 0.1-mM ARA, eicosapentaenoic acid (EPA) or DHA bound to albumin (1:1 molar ratio), and the oxylipins generated were examined using high performance liquid chromatography-tandem mass spectrometry (HPLC/MS/MS). Of 135 oxylipins screened in the media, 63 were present at >0.1 ng/mL at baseline, and 95 were present after incubation with fatty acid. Oxylipins were rapidly generated and reached maximum levels by 2-5 min. While ARA, EPA and DHA each stimulated the production of oxylipins derived from these fatty acids themselves, ARA also stimulated the production of oxylipins from endogenous 18- and 20-carbon fatty acids, including α-linolenic acid. Oxylipins generated by the lipoxygenase pathway predominated both in resting and stimulated states. Oxylipins formed via the cytochrome P450 pathway were formed primarily from DHA and EPA, but not ARA. These data indicate that HBMECs are capable of generating a plethora of bioactive lipids that have the potential to modulate BBB endothelial cell function. PMID:26439837

  11. Early alterations in blood and brain RANTES and MCP-1 expression and the effect of exercise frequency in the 3xTg-AD mouse model of Alzheimer's disease.

    PubMed

    Haskins, Morgan; Jones, Terry E; Lu, Qun; Bareiss, Sonja K

    2016-01-01

    Exercise has been shown to protect against cognitive decline and Alzheimer's disease (AD) progression, however the dose of exercise required to protect against AD is unknown. Recent studies show that the pathological processes leading to AD cause characteristic alterations in blood and brain inflammatory proteins that are associated with the progression of AD, suggesting that these markers could be used to diagnosis and monitor disease progression. The purpose of this study was to determine the impact of exercise frequency on AD blood chemokine profiles, and correlate these findings with chemokine brain expression changes in the triple transgenic AD (3xTg-AD) mouse model. Three month old 3xTg-AD mice were subjected to 12 weeks of moderate intensity wheel running at a frequency of either 1×/week or 3×/week. Blood and cortical tissue were analyzed for expression of monocyte chemotactic protein-1 (MCP-1) and regulated and normal T cell expressed and secreted (RANTES). Alterations in blood RANTES and MCP-1 expression were evident at 3 and 6 month old animals compared to WT animals. Three times per week exercise but not 1×/week exercise was effective at reversing serum and brain RANTES and MCP-1 expression to the levels of WT controls, revealing a dose dependent response to exercise. Analysis of these chemokines showed a strong negative correlation between blood and brain expression of RANTES. The results indicate that alterations in serum and brain inflammatory chemokines are evident as early signs of Alzheimer's disease pathology and that higher frequency exercise was necessary to restore blood and brain inflammatory expression levels in this AD mouse model. PMID:26547034

  12. Postmortem toxicology of drugs of abuse.

    PubMed

    Drummer, Olaf H

    2004-06-10

    Conducting toxicology on post-mortem specimens provides a number of very significant challenges to the scientist. The range of additional specimens include tissues such as decomposing blood and other tissues, hair, muscle, fat, lung, and even larvae feeding on the host require special techniques to isolate a foreign substance and allow detection without interference from the matrix. A number of drugs of abuse are unstable in the post-mortem environment that requires careful consideration when trying to interpret their significance. Heroin, morphine glucuronides, cocaine and the benzodiazepines are particularly prone to degradation. Moreover, redistributive process can significantly alter the concentration of drugs, particularly those with a higher tissue concentration than the surrounding blood. The designer amphetamines, methadone and other potent opioids will increase their concentration in blood post-mortem. These processes together with the development of tolerance means that no concentration of a drug of abuse can be interpreted in isolation without a thorough examination of the relevant circumstances and after the conduct of a post-mortem to eliminate or corroborate relevant factors that could impact on the drug concentration and the possible effect of a substance on the body. This article reviews particular toxicological issues associated with the more common drugs of abuse such as the amphetamines, cannabinoids, cocaine, opioids and the benzodiazepines. PMID:15172074

  13. Postmortem validation of MRI cortical volume measurements in MS.

    PubMed

    Popescu, Veronica; Klaver, Roel; Versteeg, Adriaan; Voorn, Pieter; Twisk, Jos W R; Barkhof, Frederik; Geurts, Jeroen J G; Vrenken, Hugo

    2016-06-01

    Grey matter (GM) atrophy is a prominent aspect of multiple sclerosis pathology and an important outcome in studies. GM atrophy measurement requires accurate GM segmentation. Several methods are used in vivo for measuring GM volumes in MS, but assessing their validity in vivo remains challenging. In this postmortem study, we evaluated the correlation between postmortem MRI cortical volume or thickness and the cortical thickness measured on histological sections. Sixteen MS brains were scanned in situ using 3DT1-weighted MRI and these images were used to measure regional cortical volume using FSL-SIENAX, FreeSurfer, and SPM, and regional cortical thickness using FreeSurfer. Subsequently, cortical thickness was measured histologically in 5 systematically sampled cortical areas. Linear regression analyses were used to evaluate the relation between MRI regional cortical volume or thickness and histological cortical thickness to determine which postprocessing technique was most valid. After correction for multiple comparisons, we observed a significant correlation with the histological cortical thickness for FSL-SIENAX cortical volume with manual editing (std. β = 0.345, adjusted R(2)  = 0.105, P = 0.005), and FreeSurfer cortical volume with manual editing (std. β = 0.379, adjusted R(2)  = 0.129, P = 0.003). In addition, there was a significant correlation between FreeSurfer cortical thickness with manual editing and histological cortical thickness (std. β = 0.381, adjusted R(2)  = 0.130, P = 0.003). The results support the use of FSL-SIENAX and FreeSurfer in cases of severe MS pathology. Interestingly none of the methods were significant in automated mode, which supports the use of manual editing to improve the automated segmentation. Hum Brain Mapp 37:2223-2233, 2016. © 2016 Wiley Periodicals, Inc. PMID:26945922

  14. Age-dependent inverse correlations in CSF and plasma amyloid-β(1-42) concentrations prior to amyloid plaque deposition in the brain of 3xTg-AD mice.

    PubMed

    Cho, Soo Min; Lee, Sejin; Yang, Seung-Hoon; Kim, Hye Yun; Lee, Michael Jisoo; Kim, Hyunjin Vincent; Kim, Jiyoon; Baek, Seungyeop; Yun, Jin; Kim, Dohee; Kim, Yun Kyung; Cho, Yakdol; Woo, Jiwan; Kim, Tae Song; Kim, YoungSoo

    2016-01-01

    Amyloid-β (Aβ) plays a critical role as a biomarker in Alzheimer's disease (AD) diagnosis. In addition to its diagnostic potential in the brain, recent studies have suggested that changes of Aβ level in the plasma can possibly indicate AD onset. In this study, we found that plasma Aβ(1-42) concentration increases with age, while the concentration of Aβ(1-42) in the cerebrospinal fluid (CSF) decreases in APPswe, PS1M146V and TauP301L transgenic (3xTg-AD) mice, if measurements were made before formation of ThS-positive plaques in the brain. Our data suggests that there is an inverse correlations between the plasma and CSF Aβ(1-42) levels until plaques form in transgenic mice's brains and that the plasma Aβ concentration possesses the diagnostic potential as a biomarker for diagnosis of early AD stages. PMID:26830653

  15. Age-dependent inverse correlations in CSF and plasma amyloid-β(1–42) concentrations prior to amyloid plaque deposition in the brain of 3xTg-AD mice

    PubMed Central

    Cho, Soo Min; Lee, Sejin; Yang, Seung-Hoon; Kim, Hye Yun; Lee, Michael Jisoo; Kim, Hyunjin Vincent; Kim, Jiyoon; Baek, Seungyeop; Yun, Jin; Kim, Dohee; Kim, Yun Kyung; Cho, Yakdol; Woo, Jiwan; Kim, Tae Song; Kim, YoungSoo

    2016-01-01

    Amyloid-β (Aβ) plays a critical role as a biomarker in Alzheimer’s disease (AD) diagnosis. In addition to its diagnostic potential in the brain, recent studies have suggested that changes of Aβ level in the plasma can possibly indicate AD onset. In this study, we found that plasma Aβ(1–42) concentration increases with age, while the concentration of Aβ(1–42) in the cerebrospinal fluid (CSF) decreases in APPswe, PS1M146V and TauP301L transgenic (3xTg-AD) mice, if measurements were made before formation of ThS-positive plaques in the brain. Our data suggests that there is an inverse correlations between the plasma and CSF Aβ(1–42) levels until plaques form in transgenic mice’s brains and that the plasma Aβ concentration possesses the diagnostic potential as a biomarker for diagnosis of early AD stages. PMID:26830653

  16. Use of Postmortem Human Dura Mater and Scalp for Deriving Human Fibroblast Cultures

    PubMed Central

    Bliss, Lindsay A.; Sams, Malik R.; Deep-Soboslay, Amy; Ren-Patterson, Renee; Jaffe, Andrew E.; Chenoweth, Josh G.; Jaishankar, Amritha; Kleinman, Joel E.; Hyde, Thomas M.

    2012-01-01

    Fibroblasts can be collected from deceased individuals, grown in culture, reprogrammed into induced pluripotent stem cells (iPSCs), and then differentiated into a multitude of cell types, including neurons. Past studies have generated iPSCs from somatic cell biopsies from either animal or human subjects. Previously, fibroblasts have only been successfully cultured from postmortem human skin in two studies. Here we present data on fibroblast cell cultures generated from 146 scalp and/or 53 dura mater samples from 146 postmortem human brain donors. In our overall sample, the odds of successful dural culture was almost two-fold compared with scalp (OR = 1.95, 95% CI: [1.01, 3.9], p = 0.047). Using a paired design within subjects for whom both tissues were available for culture (n = 53), the odds of success for culture in dura was 16-fold as compared to scalp (OR = 16.0, 95% CI: [2.1–120.6], p = 0.0007). Unattended death, tissue donation source, longer postmortem interval (PMI), and higher body mass index (BMI) were associated with unsuccessful culture in scalp (all p<0.05), but not in dura. While scalp cells proliferated more and grew more rapidly than dura cells [F (1, 46) = 12.94, p<0.008], both tissues could be generated and maintained as fibroblast cell lines. Using a random sample of four cases, we found that both postmortem scalp and dura could be successfully reprogrammed into iPSC lines. Our study demonstrates that postmortem dura mater, and to a lesser extent, scalp, are viable sources of living fibroblasts for culture that can be used to generate iPSCs. These tissues may be accessible through existing brain tissue collections, which is critical for studying disorders such as neuropsychiatric diseases. PMID:23028905

  17. The ethics of postmortem examinations in contemporary Islam.

    PubMed Central

    Rispler-Chaim, V

    1993-01-01

    Postmortem examinations have recently become common practice in Western medicine: they are used to verify the cause of death and to obtain additional scientific information on certain diseases, as well as to train medical students. For religious people of the monotheistic faiths postmortems present several ethical questions even though the advantages attributed to postmortems in the West are also acknowledged by Jews, Christians and Muslims. The Islamic way of dealing with such questions will be surveyed via contemporary fatawa (legal opinions) issued primarily by Egyptian scholars; Islamic law, which was formulated in the eighth to ninth centuries, did not speak of postmortems. I will therefore depict the means whereby contemporary scholars approach postmortems in the absence of clear legal reference. The difficulties that postmortems create for Muslims at present will be weighed against some shar i instructions which may help circumvent them. While the ethical and religious debate continues, postmortems seem to be accepted but not, however, without certain reservations. PMID:8230149

  18. The ethics of postmortem examinations in contemporary Islam.

    PubMed

    Rispler-Chaim, V

    1993-09-01

    Postmortem examinations have recently become common practice in Western medicine: they are used to verify the cause of death and to obtain additional scientific information on certain diseases, as well as to train medical students. For religious people of the monotheistic faiths postmortems present several ethical questions even though the advantages attributed to postmortems in the West are also acknowledged by Jews, Christians and Muslims. The Islamic way of dealing with such questions will be surveyed via contemporary fatawa (legal opinions) issued primarily by Egyptian scholars; Islamic law, which was formulated in the eighth to ninth centuries, did not speak of postmortems. I will therefore depict the means whereby contemporary scholars approach postmortems in the absence of clear legal reference. The difficulties that postmortems create for Muslims at present will be weighed against some shar i instructions which may help circumvent them. While the ethical and religious debate continues, postmortems seem to be accepted but not, however, without certain reservations. PMID:8230149

  19. Seasonal variation of postmortem microbial communities.

    PubMed

    Carter, David O; Metcalf, Jessica L; Bibat, Alexander; Knight, Rob

    2015-06-01

    Body-associated microbes were recently shown to change significantly during decomposition, undergoing an ecological succession in experimental conditions using rodent and swine models. We investigated microbial succession in soils associated with swine carcasses under experimental field conditions in summer and winter. We demonstrate that these postmortem microbial communities change in a specific, reproducible fashion, and that soil microbes represent a significant component of the postmortem microbial community, contrary to widespread belief in forensic science. However, the effects of decomposition on soil microbial communities were different in summer and winter. We suggest that the microbial ecological succession will be useful in medicolegal death investigation; however, observations in winter might not be applicable to summer, which indicates a need for a greater understanding of the seasonality of decomposition. PMID:25737335

  20. [Post-mortem study of laryngotracheal lesions produced by prolonged intubation and/or tracheotomy].

    PubMed

    Esteller Moré, E; Ibáñez-Nolla, J; García-Hernández, F; Carrasco-García, M A; León-Regidor, M A; Díaz-Boladeras, R M; Orus-Dotu, C; Ademà-Alcover, J M; Nolla-Salas, M

    1997-10-01

    Injuries of the laryngotracheal axis caused by prolonged intubation in critically ill patients raise the issue of the timing of tracheotomy in intubated patients. In 1992 a prospective study was begun in intensive care patients with intubation lasting more than 48 hours. Eight months later, post-mortem data on the laryngotracheal axis of deceased patients was added to our prospective study protocol. The study was closed with 125 cases (52 deceased). The clinical data of 73 surviving patients was compared with that of 18 post-mortem cases. The macroscopic results of the post-mortem study are summarized by grading the lesions according to a personal modification of the Lindholm classification. All cases had laryngotracheal injuries. Only 15% of the lesions were located in the tracheal region. Five cases were classified as grade 2, with an average orotracheal intubation of 9 days, 9 cases as grade 3 with 15 days intubation, and 4 cases as grade 4 with 21 days intubation. We concluded that the severity of laryngotracheal injuries in the early post-mortem exploration was related with the duration of intubation. PMID:9489156

  1. Human anti-Aβ IgGs target conformational epitopes on synthetic dimer assemblies and the AD brain-derived peptide.

    PubMed

    Welzel, Alfred T; Williams, Angela D; McWilliams-Koeppen, Helen P; Acero, Luis; Weber, Alfred; Blinder, Veronika; Mably, Alex; Bunk, Sebastian; Hermann, Corinna; Farrell, Michael A; Ehrlich, Hartmut J; Schwarz, Hans P; Walsh, Dominic M; Solomon, Alan; O'Nuallain, Brian

    2012-01-01

    Soluble non-fibrillar assemblies of amyloid-beta (Aβ) and aggregated tau protein are the proximate synaptotoxic species associated with Alzheimer's disease (AD). Anti-Aβ immunotherapy is a promising and advanced therapeutic strategy, but the precise Aβ species to target is not yet known. Previously, we and others have shown that natural human IgGs (NAbs) target diverse Aβ conformers and have therapeutic potential. We now demonstrate that these antibodies bound with nM avidity to conformational epitopes on plate-immobilized synthetic Aβ dimer assemblies, including synaptotoxic protofibrils, and targeted these conformers in solution. Importantly, NAbs also recognized Aβ extracted from the water-soluble phase of human AD brain, including species that migrated on denaturing PAGE as SDS-stable dimers. The critical reliance on Aβ's conformational state for NAb binding, and not a linear sequence epitope, was confirmed by the antibody's nM reactivity with plate-immobilized protofibrills, and weak uM binding to synthetic Aβ monomers and peptide fragments. The antibody's lack of reactivity against a linear sequence epitope was confirmed by our ability to isolate anti-Aβ NAbs from intravenous immunoglobulin using affinity matrices, immunoglobulin light chain fibrils and Cibacron blue, which had no sequence similarity with the peptide. These findings suggest that further investigations on the molecular basis and the therapeutic/diagnostic potential of anti-Aβ NAbs are warranted. PMID:23209707

  2. Human Anti-Aβ IgGs Target Conformational Epitopes on Synthetic Dimer Assemblies and the AD Brain-Derived Peptide

    PubMed Central

    Welzel, Alfred T.; Williams, Angela D.; McWilliams-Koeppen, Helen P.; Acero, Luis; Weber, Alfred; Blinder, Veronika; Mably, Alex; Bunk, Sebastian; Hermann, Corinna; Farrell, Michael A.; Ehrlich, Hartmut J.; Schwarz, Hans P.; Walsh, Dominic M.; Solomon, Alan; O’Nuallain, Brian

    2012-01-01

    Soluble non-fibrillar assemblies of amyloid-beta (Aβ) and aggregated tau protein are the proximate synaptotoxic species associated with Alzheimer’s disease (AD). Anti-Aβ immunotherapy is a promising and advanced therapeutic strategy, but the precise Aβ species to target is not yet known. Previously, we and others have shown that natural human IgGs (NAbs) target diverse Aβ conformers and have therapeutic potential. We now demonstrate that these antibodies bound with nM avidity to conformational epitopes on plate-immobilized synthetic Aβ dimer assemblies, including synaptotoxic protofibrils, and targeted these conformers in solution. Importantly, NAbs also recognized Aβ extracted from the water-soluble phase of human AD brain, including species that migrated on denaturing PAGE as SDS-stable dimers. The critical reliance on Aβ’s conformational state for NAb binding, and not a linear sequence epitope, was confirmed by the antibody’s nM reactivity with plate-immobilized protofibrills, and weak uM binding to synthetic Aβ monomers and peptide fragments. The antibody’s lack of reactivity against a linear sequence epitope was confirmed by our ability to isolate anti-Aβ NAbs from intravenous immunoglobulin using affinity matrices, immunoglobulin light chain fibrils and Cibacron blue, which had no sequence similarity with the peptide. These findings suggest that further investigations on the molecular basis and the therapeutic/diagnostic potential of anti-Aβ NAbs are warranted. PMID:23209707

  3. Postmortem diagnosis and toxicological validation of illicit substance use.

    PubMed

    Lehrmann, Elin; Afanador, Zoan R; Deep-Soboslay, Amy; Gallegos, Gloria; Darwin, William D; Lowe, Ross H; Barnes, Allan J; Huestis, Marilyn A; Cadet, Jean L; Herman, Mary M; Hyde, Thomas M; Kleinman, Joel E; Freed, William J

    2008-03-01

    The present study examines the diagnostic challenges of identifying ante-mortem illicit substance use in human postmortem cases. Substance use, assessed by clinical case history reviews, structured next-of-kin interviews, by general toxicology of blood, urine and/or brain, and by scalp hair testing, identified 33 cocaine, 29 cannabis, 10 phencyclidine and nine opioid cases. Case history identified 42% cocaine, 76% cannabis, 10% phencyclidine and 33% opioid cases. Next-of-kin interviews identified almost twice as many cocaine and cannabis cases as Medical Examiner (ME) case histories, and were crucial in establishing a detailed lifetime substance use history. Toxicology identified 91% cocaine, 68% cannabis, 80% phencyclidine and 100% opioid cases, with hair testing increasing detection for all drug classes. A cocaine or cannabis use history was corroborated by general toxicology with 50% and 32% sensitivity, respectively, and with 82% and 64% sensitivity by hair testing. Hair testing corroborated a positive general toxicology for cocaine and cannabis with 91% and 100% sensitivity, respectively. Case history corroborated hair toxicology with 38% sensitivity for cocaine and 79% sensitivity for cannabis, suggesting that both case history and general toxicology underestimated cocaine use. Identifying ante-mortem substance use in human postmortem cases are key considerations in case diagnosis and for characterization of disorder-specific changes in neurobiology. The sensitivity and specificity of substance use assessments increased when ME case history was supplemented with structured next-of-kin interviews to establish a detailed lifetime substance use history, while comprehensive toxicology, and hair testing in particular, increased detection of recent illicit substance use. PMID:18201295

  4. Essentials of forensic post-mortem MR imaging in adults

    PubMed Central

    Ruder, T D; Thali, M J; Hatch, G M

    2014-01-01

    Post-mortem MR (PMMR) imaging is a powerful diagnostic tool with a wide scope in forensic radiology. In the past 20 years, PMMR has been used as both an adjunct and an alternative to autopsy. The role of PMMR in forensic death investigations largely depends on the rules and habits of local jurisdictions, availability of experts, financial resources, and individual case circumstances. PMMR images are affected by post-mortem changes, including position-dependent sedimentation, variable body temperature and decomposition. Investigators must be familiar with the appearance of normal findings on PMMR to distinguish them from disease or injury. Coronal whole-body images provide a comprehensive overview. Notably, short tau inversion–recovery (STIR) images enable investigators to screen for pathological fluid accumulation, to which we refer as “forensic sentinel sign”. If scan time is short, subsequent PMMR imaging may be focussed on regions with a positive forensic sentinel sign. PMMR offers excellent anatomical detail and is especially useful to visualize pathologies of the brain, heart, subcutaneous fat tissue and abdominal organs. PMMR may also be used to document skeletal injury. Cardiovascular imaging is a core area of PMMR imaging and growing evidence indicates that PMMR is able to detect ischaemic injury at an earlier stage than traditional autopsy and routine histology. The aim of this review is to present an overview of normal findings on forensic PMMR, provide general advice on the application of PMMR and summarise the current literature on PMMR imaging of the head and neck, cardiovascular system, abdomen and musculoskeletal system. PMID:24191122

  5. Postmortem changes of ingested thinner components in tissues.

    PubMed

    Kimura, K; Nagata, T; Kato, K; Kudo, K; Imamura, T

    1991-06-01

    Postmortem changes of thinner components in body tissues were examined in rats, orally given 1 ml of standard thinner solution, which was prepared by mixing toluene, ethyl acetate and isobutanol in the proportion of 8:1:1. Analysis was made by gas chromatography combined with the head space method. Three thinner components and ethanol, a metabolite of ethyl acetate, were detected in the gastric contents of all rats up until 48 hours after death. An increase in the concentration of toluene was found in the blood, lung, kidney, liver, brain and abdominal muscle with the lapse of time. On the other hand, no changes were observed in the thigh muscle throughout the 48-hour period. Isobutanol showed a similar increasing pattern to toluene, with little or no changes in the brain or in the thigh muscle. Ethyl acetate was not detected in any tissues throughout the study but it was found in the gastric contents. The results indicate that every thinner component ingested, gradually diffuses into the surrounding tissues through the stomach wall after death, and that only muscle tissue remote from the abdominal cavity, together with the gastric contents, should be analyzed for a correct diagnosis of thinner ingestion. PMID:1920928

  6. Antemortem vitreous potassium may strengthen postmortem interval estimates.

    PubMed

    Kokavec, Jan; Min, San H; Tan, Mei H; Gilhotra, Jagjit S; Newland, Henry S; Durkin, Shane R; Casson, Robert J

    2016-06-01

    The purpose of this letter is to highlight that postmortem interval estimates using vitreous potassium concentrations may be further optimised by calibration against antemortem vitreous samples. PMID:27080618

  7. Angiotensin-converting enzyme levels and activity in Alzheimer's disease: differences in brain and CSF ACE and association with ACE1 genotypes

    PubMed Central

    Miners, Scott; Ashby, Emma; Baig, Shabnam; Harrison, Rachel; Tayler, Hannah; Speedy, Elizabeth; Prince, Jonathan A; Love, Seth; Kehoe, Patrick G

    2009-01-01

    Angiotensin-converting enzyme (ACE) has been implicated in Alzheimer's disease (AD): ACE1 variations influence plasma ACE and risk of AD, and ACE is increased in AD brain. We measured frontal ACE level and activity in 89 AD and 51 control brains, and post-mortem CSF from 101 cases and 19 controls. Neuron-specific enolase (NSE) level and Braak stage were used to indicate neuronal preservation and disease progression. We genotyped the common ACE insertion/deletion polymorphism, rs4343, rs1800764 and rs4921. ACE activity was elevated in AD and correlated with Braak stage. Crude ACE levels were unchanged but adjustment for NSE suggested increased neuronal ACE production with Braak stage. Exposing SH-SY-5Y neurons to oligomeric Aβ1-42 increased ACE level and activity, suggesting Aβ may upregulate ACE in AD. In CSF, ACE level but not activity was reduced in AD. ACE1 genotype did not predict ACE level or activity in brain or CSF. ACE activity and neuronal production increase in AD brain, possibly in response to Aβ. Peripheral measurements do not reflect ACE activity in the brain. PMID:19956428

  8. Pre- and postmortem imaging of transplanted cells

    PubMed Central

    Andrzejewska, Anna; Nowakowski, Adam; Janowski, Miroslaw; Bulte, Jeff WM; Gilad, Assaf A; Walczak, Piotr; Lukomska, Barbara

    2015-01-01

    Therapeutic interventions based on the transplantation of stem and progenitor cells have garnered increasing interest. This interest is fueled by successful preclinical studies for indications in many diseases, including the cardiovascular, central nervous, and musculoskeletal system. Further progress in this field is contingent upon access to techniques that facilitate an unambiguous identification and characterization of grafted cells. Such methods are invaluable for optimization of cell delivery, improvement of cell survival, and assessment of the functional integration of grafted cells. Following is a focused overview of the currently available cell detection and tracking methodologies that covers the entire spectrum from pre- to postmortem cell identification. PMID:26366076

  9. Postmortem Changes in Animal Carcasses and Estimation of the Postmortem Interval.

    PubMed

    Brooks, J W

    2016-09-01

    A thorough understanding of the physical and chemical changes that occur in the body after death is critical for accurate interpretation of gross and microscopic pathology at autopsy. Furthermore, knowledge of the postmortem processes and the factors that affect them will aid in the estimation of the postmortem interval (PMI). The estimation of the PMI is important in many human and animal death investigations. Despite many decades of research, accuracy in estimation of the time of death has not significantly improved, and no single method can be reliably used to accurately estimate the time of death. Great care should be taken when formulating such an estimate, for it is dependent on multiple circumstantial and environmental factors, and the accuracy and precision of the estimate decrease as the PMI increases. The majority of the research in the field has been conducted on human bodies, but many relevant conclusions may be drawn regarding the expected postmortem changes in animals and the estimation of the PMI. The veterinary pathologist must use great caution when attempting to extrapolate data and apply formulas designed for use in humans. Methods reviewed include gross changes, microscopic changes, temperature-based methods, postmortem chemistry, molecular methods, microbial assay, ocular changes, radiography, entomology, and others. Although only several of these methods are currently practical for use in the workup of cases, it is expected that future research will result in improved techniques with enhanced accuracy in the estimation of the PMI, which will benefit both human and veterinary forensic investigations. PMID:26945004

  10. Characterization of gene expression profiling of mouse tissues obtained during the postmortem interval.

    PubMed

    Sobue, Sayaka; Sakata, Keita; Sekijima, Yuki; Qiao, Shanlou; Murate, Takashi; Ichihara, Masatoshi

    2016-06-01

    Attempts to establish a tissue bank from autopsy samples have led to uncovering of the secrets of many diseases. Here, we examined the length of time that the RNA from postmortem tissues is available for microarray analysis and reported the gene expression profile for up- and down-regulated genes during the postmortem interval. We extracted RNA from fresh-frozen (FF) and formalin-fixed paraffin-embedded (FFPE) brains and livers of three different groups of mice: 1) mice immediately after death, 2) mice that were stored at room temperature for 3h after death, and 3) mice that were stored at 4°C for 18h after death, as this storage resembles the human autopsy process in Japan. The RNA quality of the brain and the liver was maintained up to 18h during the postmortem interval. Based on the microarray analysis, we selected genes that were altered by >1.3-fold or <0.77-fold and classified these genes using hierarchical cluster analysis following DAVID gene ontology analysis. These studies revealed that cytoskeleton-related genes were enriched in the set of up-regulated genes, while serine protease inhibitors were enriched in the set of down-regulated genes. Interestingly, although the RNA quality was maintained due to high RNA integrity number (RIN) values, up-regulated genes were not validated by quantitative PCR, suggesting that these genes may become fragmented or modified by an unknown mechanism. Taken together, our findings suggest that under typical autopsy conditions, gene expression profiles that reflect disease pathology can be examined by understanding comprehensive recognition of postmortem fluctuation of gene expression. PMID:27185020

  11. [Two cases of hydrophobia in the Republic of Tatarstan: in vivo and postmortem laboratory diagnosis].

    PubMed

    Khismatullina, N A; Gulyukin, A M; Gulyukin, M I; Ivanov, A V; Sabirova, V V; Yuzhakov, A G; Alexandrova, N M; Samerkhanov, I I; Aliper, T I

    2015-01-01

    The results of rabies in vivo and postmortem laboratory detection in two cases registered in the Republic of Tatarstan are reported: a victim bitten by a wolf in 2002 and another one bitten by a stray dog on Goa Island, India, in 2013. In the patient bitten by a wolf cornea imprints studies using the method of fluorescent antibodies (MFA) showed rabies-positive result 6 days before the patient's death. The results were confirmed by postmortem examination of different parts of the brain and salivary glands using the MFA, enzyme-linked immunosorbent assay (ELISA), optical microscopy, and bioassay methods. In the patient bitten by a stray dog the rabies virus specific antigen was detected by eye cornea studies using the MFA method and saliva studies using the ELISA. The rabies virus genome was also isolated from saliva and tear fluid using nested reverse-transcription polymerase chain reaction (RT-PCR) 9 days before the patient's death. The in viva studies results were consistent with the postmortem study of different parts of the brain using the MFA, enzyme-linked immunosorbent assay (ELISA), optical microscopy, and bioassay methods. All the infection-positive results of both in viva and postmortem studies were consistent with the clinical studies, i.e. rabies diagnosis was confirmed. The analysis of the rabies virus gene G fragment nucleotide sequence of 238 nd length showed a slight difference between the studied isolates (2 rabies) and the RABV AY9563I9 (1.68%), difference by 10.5% from the Vnukovo-32 vaccine strains and by 10.9% from the SAD B19 rabies strain, respectively (rabies viruses of 1st genotype). It was also significantly different from the lissaviruses of 2,4,5, and 6 genotypes (21 .0-32.7%). The obtained results indicate phylogenetic closeness of the studied isolates (2 rabies) with the RABV AY956319 rabies virus strain belonging to the 1st genotype. PMID:26182652

  12. Age-Dependent Regulation of the Blood-Brain Barrier Influx/Efflux Equilibrium of Amyloid-β Peptide in a Mouse Model of Alzheimer's Disease (3xTg-AD).

    PubMed

    Do, Tuan Minh; Dodacki, Agnès; Alata, Wael; Calon, Frederic; Nicolic, Sophie; Scherrmann, Jean-Michel; Farinotti, Robert; Bourasset, Fanchon

    2015-01-01

    The involvement of transporters located at the blood-brain barrier (BBB) has been suggested in the control of cerebral Aβ levels, and thereby in Alzheimer's disease (AD). However, little is known about the regulation of these transporters at the BBB in animal models of AD. In this study, we investigated the BBB expression of Aβ influx (Rage) and efflux (Abcb1-Abcg2-Abcg4-Lrp-1) transporters and cholesterol transporter (Abca1) in 3-18-month-old 3xTg-AD and control mice. The age-dependent effect of BBB transporters regulation on the brain uptake clearance (Clup) of [3H]cholesterol and [3H]Aβ1 - 40 was then evaluated in these mice, using the in situ brain perfusion technique. Our data suggest that transgenes expression led to the BBB increase in Aβ influx receptor (Rage) and decrease in efflux receptor (Lrp-1). Our data also indicate that mice have mechanisms counteracting this increased net influx. Indeed, Abcg4 and Abca1 are up regulated in 3- and 3/6-month-old 3xTg-AD mice, respectively. Our data show that the balance between the BBB influx and efflux of Aβ is maintained in 3 and 6-month-old 3xTg-AD mice, suggesting that Abcg4 and Abca1 control the efflux of Aβ through the BBB by a direct (Abcg4) or indirect (Abca1) mechanism. At 18 months, the BBB Aβ efflux is significantly increased in 3xTg-AD mice compared to controls. This could result from the significant up-regulation of both Abcg2 and Abcb1 in 3xTg-AD mice compared to control mice. Thus, age-dependent regulation of several Aβ and cholesterol transporters at the BBB could ultimately limit the brain accumulation of Aβ. PMID:26484906

  13. Detection of Alzheimer’s disease amyloid-beta plaque deposition by deep brain impedance profiling

    NASA Astrophysics Data System (ADS)

    Béduer, Amélie; Joris, Pierre; Mosser, Sébastien; Fraering, Patrick C.; Renaud, Philippe

    2015-04-01

    Objective. Alzheimer disease (AD) is the most common form of neurodegenerative disease in elderly people. Toxic brain amyloid-beta (Aß) aggregates and ensuing cell death are believed to play a central role in the pathogenesis of the disease. In this study, we investigated if we could monitor the presence of these aggregates by performing in situ electrical impedance spectroscopy measurements in AD model mice brains. Approach. In this study, electrical impedance spectroscopy measurements were performed post-mortem in APPPS1 transgenic mice brains. This transgenic model is commonly used to study amyloidogenesis, a pathological hallmark of AD. We used flexible probes with embedded micrometric electrodes array to demonstrate the feasibility of detecting senile plaques composed of Aß peptides by localized impedance measurements. Main results. We particularly focused on deep brain structures, such as the hippocampus. Ex vivo experiments using brains from young and old APPPS1 mice lead us to show that impedance measurements clearly correlate with the percentage of Aβ plaque load in the brain tissues. We could monitor the effects of aging in the AD APPPS1 mice model. Significance. We demonstrated that a localized electrical impedance measurement constitutes a valuable technique to monitor the presence of Aβ-plaques, which is complementary with existing imaging techniques. This method does not require prior Aβ staining, precluding the risk of variations in tissue uptake of dyes or tracers, and consequently ensuring reproducible data collection.

  14. F-18 Stilbenes As PET Imaging Agents For Detecting β-Amyloid Plaques In The Brain

    PubMed Central

    Zhang, Wei; Oya, Shunichi; Kung, Mei-Ping; Hou, Catherine; Maier, Donna L.; Kung, Hank F.

    2008-01-01

    Imaging agents targeting β,-amyloid (Aβ) may be useful for diagnosis and treatment of patients with Alzheimer’s disease (AD). Compounds 3e and 4e are fluorinated stilbene derivatives displaying high binding affinities for Aβ plaques in AD brain homogenates (Ki = 15 ± 6 and 5.0 ± 1.2 nM, respectively). In vivo biodistributions of [18F]3e and [18F]4e in normal mice exhibited excellent brain penetrations (5.55 and 9.75 % dose/g at 2 min) and rapid brain washouts were observed, especially for [18F]4e (0.72% dose/g at 60 min). They also showed in vivo plaque labeling in APP/PS1 or Tg2576 transgenic mice, animal models for AD. Autoradiography of postmortem AD brain sections and AD homogenate binding studies confirmed the selective and specific binding properties to Aβ plaques. In conclusion, the preliminary results strongly suggest that these fluorinated stilbene derivatives, [18F]3e and [18F]4e, are suitable candidates as Aβ plaque imaging agents for studying patients with AD. PMID:16162001

  15. High-resolution Structural Magnetic Resonance Imaging of the Human Subcortex In Vivo and Postmortem.

    PubMed

    McKetton, Larissa; Williams, Joy; Viviano, Joseph D; Yücel, Yeni H; Gupta, Neeru; Schneider, Keith A

    2015-01-01

    The focus of this study was to test the resolution limits of structural MRI of a postmortem brain compared to living human brains. The resolution of structural MRI in vivo is ultimately limited by physiological noise, including pulsation, respiration and head movement. Although imaging hardware continues to improve, it is still difficult to resolve structures on the millimeter scale. For example, the primary visual sensory pathways synapse at the lateral geniculate nucleus (LGN), a visual relay and control nucleus in the thalamus that normally is organized into six interleaved monocular layers. Neuroimaging studies have not been able to reliably distinguish these layers due their small size that are less than 1 mm thick. The resolving limit of structural MRI, in a postmortem brain was tested using multiple images averaged over a long duration (~24 h). The purpose was to test whether it was possible to resolve the individual layers of the LGN in the absence of physiological noise. A proton density (PD)(1) weighted pulse sequence was used with varying resolution and other parameters to determine the minimum number of images necessary to be registered and averaged to reliably distinguish the LGN and other subcortical regions. The results were also compared to images acquired in living human brains. In vivo subjects were scanned in order to determine the additional effects of physiological noise on the minimum number of PD scans needed to differentiate subcortical structures, useful in clinical applications. PMID:26779880

  16. Examination of postmortem retinal folds: A non-invasive study.

    PubMed

    Oshima, Toru; Yoshikawa, Hiroshi; Ohtani, Maki; Mimasaka, Sohtaro

    2015-02-01

    The postmortem retinal fold has been previously documented, but its mechanism of formation is not known. All previous studies of the fold involved invasive techniques and the postmortem ocular fundus has yet to be non-invasively examined. Our study used the non-invasive techniques of monocular indirect ophthalmoscopy and ocular echography to examine 79 postmortem eyes of 42 bodies. We examined whether the postmortem retinal fold was associated with postmortem time, position, and/or age. Age was significantly associated with postmortem retinal fold formation (Mann-Whitney U test, P = 0.013), which led us to examine the effect of posterior vitreous detachment (PVD) on retinal folds. The absence of a PVD was statistically associated with the presence of a retinal fold (Fisher's exact test, P < 0.0001). Interestingly, the presence of a PVD was also significantly correlated with retinal fold height (Mann-Whitney U test, P < 0.0001). Therefore, we hypothesized that retinal folds result from postmortem vitreoretinal traction caused by eyeball flaccidity. We also believe that the loss of retinochoroidal hydrostatic pressure plays a role. It is important that forensic pathologists not confuse a postmortem retinal fold with traumatic retinal detachment or perimacular retinal folds caused by child abuse. When child abuse is suspected, forensic pathologists should perform enucleation and a subsequent histological examination for confirmation. PMID:25623189

  17. Antemortem stress regulates protein acetylation and glycolysis in postmortem muscle.

    PubMed

    Li, Zhongwen; Li, Xin; Wang, Zhenyu; Shen, Qingwu W; Zhang, Dequan

    2016-07-01

    Although exhaustive research has established that preslaughter stress is a major factor contributing to pale, soft, exudative (PSE) meat, questions remain regarding the biochemistry of postmortem glycolysis. In this study, the influence of preslaughter stress on protein acetylation in relationship to glycolysis was studied. The data show that antemortem swimming significantly enhanced glycolysis and the total acetylated proteins in postmortem longissimus dorsi (LD) muscle of mice. Inhibition of protein acetylation by histone acetyltransferase (HAT) inhibitors eliminated stress induced increase in glycolysis. Inversely, antemortem injection of histone deacetylase (HDAC) inhibitors, trichostatin A (TSA) and nicotinamide (NAM), further increased protein acetylation early postmortem and the glycolysis. These data provide new insight into the biochemistry of postmortem glycolysis by showing that protein acetylation regulates glycolysis, which may participate in the regulation of preslaughter stress on glycolysis in postmortem muscle. PMID:26920270

  18. Age-associated changes of brain copper, iron, and zinc in Alzheimer's disease and dementia with Lewy bodies.

    PubMed

    Graham, Stewart F; Nasaruddin, Muhammad Bin; Carey, Manus; Holscher, Christian; McGuinness, Bernadette; Kehoe, Patrick G; Love, Seth; Passmore, Peter; Elliott, Christopher T; Meharg, Andrew A; Green, Brian D

    2014-01-01

    Disease-, age-, and gender-associated changes in brain copper, iron, and zinc were assessed in postmortem neocortical tissue (Brodmann area 7) from patients with moderate Alzheimer's disease (AD) (n = 14), severe AD (n = 28), dementia with Lewy bodies (n = 15), and normal age-matched control subjects (n = 26). Copper was lower (20%; p < 0.001) and iron higher (10-16%; p < 0.001) in severe AD compared with controls. Intriguingly significant Group*Age interactions were observed for both copper and iron, suggesting gradual age-associated decline of these metals in healthy non-cognitively impaired individuals. Zinc was unaffected in any disease pathologies and no age-associated changes were apparent. Age-associated changes in brain elements warrant further investigation. PMID:25024342

  19. Post-mortem cytogenomic investigations in patients with congenital malformations.

    PubMed

    Dias, Alexandre Torchio; Zanardo, Évelin Aline; Dutra, Roberta Lelis; Piazzon, Flavia Balbo; Novo-Filho, Gil Monteiro; Montenegro, Marilia Moreira; Nascimento, Amom Mendes; Rocha, Mariana; Madia, Fabricia Andreia Rosa; Costa, Thais Virgínia Moura Machado; Milani, Cintia; Schultz, Regina; Gonçalves, Fernanda Toledo; Fridman, Cintia; Yamamoto, Guilherme Lopes; Bertola, Débora Romeo; Kim, Chong Ae; Kulikowski, Leslie Domenici

    2016-08-01

    Congenital anomalies are the second highest cause of infant deaths, and, in most cases, diagnosis is a challenge. In this study, we characterize patterns of DNA copy number aberrations in different samples of post-mortem tissues from patients with congenital malformations. Twenty-eight patients undergoing autopsy were cytogenomically evaluated using several methods, specifically, Multiplex Ligation-dependent Probe Amplification (MLPA), microsatellite marker analysis with a MiniFiler kit, FISH, a cytogenomic array technique and bidirectional Sanger sequencing, which were performed on samples of different tissues (brain, heart, liver, skin and diaphragm) preserved in RNAlater, in formaldehyde or by paraffin-embedding. The results identified 13 patients with pathogenic copy number variations (CNVs). Of these, eight presented aneuploidies involving chromosomes 13, 18, 21, X and Y (two presented inter- and intra-tissue mosaicism). In addition, other abnormalities were found, including duplication of the TYMS gene (18p11.32); deletion of the CHL1 gene (3p26.3); deletion of the HIC1 gene (17p13.3); and deletion of the TOM1L2 gene (17p11.2). One patient had a pathogenic missense mutation of g.8535C>G (c.746C>G) in exon 7 of the FGFR3 gene consistent with Thanatophoric Dysplasia type I. Cytogenomic techniques were reliable for the analysis of autopsy material and allowed the identification of inter- and intra-tissue mosaicism and a better understanding of the pathogenesis of congenital malformations. PMID:27450648

  20. Postmortem and perimortem cesarean section: historical, religious and ethical considerations.

    PubMed

    Fadel, Hossam E

    2011-12-01

    Guillimeau was the first to use the term cesarean section (CS) in 1598, but this name became universal only in the 20th century. The many theories of the origin of this name will be discussed. This surgery has been reported to be performed in all cultures dating to ancient times. In the past, it was mainly done to deliver a live baby from a dead mother, hence the name postmortem CS (PMCS). Many heroes are reported to have been delivered this way. Old Jewish sacred books have made references to abdominal delivery. It was especially encouraged and often mandated in Catholicism. There is evidence that the operation was done in Muslim countries in the middle ages. Islamic rulings support the performance of PMCS. Now that most maternal deaths occur in the hospital, perimortem CS (PRMCS) is recommended for the delivery of a fetus after 24 weeks from a pregnant woman with cardiac arrest. It is believed that emergent delivery within four minutes of initiation of cardiopulmonary resuscitation (CPR) improves the chances of success of maternal resuscitation and survival and increases the chance of delivering a neurologically intact neonate. It is agreed that physicians are not to be held legally liable for the performance of PMCS and PRMCS regardless of the outcome. The ethical aspects of these operations are also discussed including a discussion about PMCS for the delivery of women who have been declared brain dead. PMID:23610509

  1. Postmortem and Perimortem Cesarean Section: Historical, Religious and Ethical Considerations

    PubMed Central

    Fadel, Hossam E.

    2012-01-01

    Guillimeau was the first to use the term cesarean section (CS) in 1598, but this name became universal only in the 20th century. The many theories of the origin of this name will be discussed. This surgery has been reported to be performed in all cultures dating to ancient times. In the past, it was mainly done to deliver a live baby from a dead mother, hence the name postmortem CS (PMCS). Many heroes are reported to have been delivered this way. Old Jewish sacred books have made references to abdominal delivery. It was especially encouraged and often mandated in Catholicism. There is evidence that the operation was done in Muslim countries in the middle ages. Islamic rulings support the performance of PMCS. Now that most maternal deaths occur in the hospital, perimortem CS (PRMCS) is recommended for the delivery of a fetus after 24 weeks from a pregnant woman with cardiac arrest. It is believed that emergent delivery within four minutes of initiation of cardiopulmonary resuscitation (CPR) improves the chances of success of maternal resuscitation and survival and increases the chance of delivering a neurologically intact neonate. It is agreed that physicians are not to be held legally liable for the performance of PMCS and PRMCS regardless of the outcome. The ethical aspects of these operations are also discussed including a discussion about PMCS for the delivery of women who have been declared brain dead. PMID:23610509

  2. Estimation of the Postmortem Duration of Mouse Tissue by Electron Spin Resonance Spectroscopy

    PubMed Central

    Ito, Shinobu; Mori, Tomohisa; Kanazawa, Hideko; Sawaguchi, Toshiko

    2011-01-01

    Electron spin resonance (ESR) method is a simple method for detecting various free radicals simultaneously and directly. However, ESR spin trap method is unsuited to analyze weak ESR signals in organs because of water-induced dielectric loss (WIDL). To minimize WIDL occurring in biotissues and to improve detection sensitivity to free radicals in tissues, ESR cuvette was modified and used with 5,5-dimethtyl-1-pyrroline N-oxide (DMPO). The tissue samples were mouse brain, hart, lung, liver, kidney, pancreas, muscle, skin, and whole blood, where various ESR spin adduct signals including DMPO-ascorbyl radical (AsA∗), DMPO-superoxide anion radical (OOH), and DMPO-hydrogen radical (H) signal were detected. Postmortem changes in DMPO-AsA∗ and DMPO-OOH were observed in various tissues of mouse. The signal peak of spin adduct was monitored until the 205th day postmortem. DMPO-AsA∗ in liver (y = 113.8–40.7 log (day), R1 = −0.779, R2 = 0.6, P < .001) was found to linearly decrease with the logarithm of postmortem duration days. Therefore, DMPO-AsA∗ signal may be suitable for detecting an oxidation stress tracer from tissue in comparison with other spin adduct signal on ESR spin trap method. PMID:21776268

  3. Fatty acid composition of the postmortem prefrontal cortex of adolescent male and female suicide victims.

    PubMed

    McNamara, Robert K; Jandacek, Ronald; Rider, Therese; Tso, Patrick; Dwivedi, Yogesh; Roberts, Rosalinda C; Conley, Robert R; Pandey, Ghanshyam N

    2009-01-01

    Prior epidemiological, prospective intervention, and peripheral and central fatty acid composition studies suggest that omega-3 fatty acid deficiency may be associated with the pathoaetiology of depression and suicide. In the present study, we determined the fatty acid composition of the postmortem prefrontal cortex (PFC) of adolescent male and female suicide victims and age-matched controls. Fatty acid composition (wt% total fatty acids) and concentrations (micromol/g) were determined in the postmortem PFC (Brodmann area 10) of male and female adolescent (aged 13-20 years) suicide victims (n=20) and age-matched controls (n=20) by gas chromatography. None of the major polyunsaturated fatty acids including the principle brain omega-3 fatty acid, docosahexaenoic acid (DHA), monounsaturated fatty acids, or saturated fatty acids differed significantly between adolescent suicide victims and controls before or after segregation by gender. The arachidonic acid (AA, 20:4n-6): DHA ratio and adrenic acid (22:4n-6) composition were negatively correlated with age at death in controls but not in suicides, and males exhibited a greater AA:DHA ratio irrespective of cause-of-death. These results demonstrate that adolescent male and female suicide victims do not exhibit DHA deficits in the postmortem PFC relative to age-matched controls, and suggest that suicide victims do not exhibit the normal age-related decrease in adrenic acid composition and the AA:DHA ratio. PMID:19064316

  4. Can postmortem computed tomography detect antemortem hypoxic-ischemic encephalopathy?

    PubMed

    Shirota, Go; Ishida, Masanori; Shintani, Yukako; Abe, Hiroyuki; Ikemura, Masako; Fukayama, Masashi; Gonoi, Wataru

    2016-09-01

    The purpose of this study was to evaluate the usefulness of brain postmortem computed tomography (PMCT) findings for the detection of global hypoxia or hypoperfusion leading to hypoxic-ischemic encephalopathy (HIE) prior to death. Cadavers of individuals who died from non-traumatic causes were subjected to PMCT and pathological autopsy. Cases with an episode of cardiopulmonary arrest, hypoxia, or hypoperfusion that required intensive respiratory management at least 24 h before death and exhibited findings of HIE in conventional autopsy (HIE group, n = 6) were compared with those without such episodes prior to death (control group; overall, n = 37; age-matched, n = 8) with regard to four parameters: (1) width of the central sulcus (CS), (2) attenuation difference at the basal ganglia (BG) level, (3) attenuation difference between cerebral gray matter (GM) and cerebral white matter (WM), and (4) attenuation difference between cerebellar GM and cerebral GM. The results revealed significant differences in the width of the CS (P < 0.001), attenuation difference at the BG level (P < 0.001), and attenuation difference between cerebral GM and cerebral WM (P = 0.009) between the HIE group and the overall control group. When the age-matched control group and the HIE group were compared, there was a significant difference in the width of the CS (P = 0.026) and attenuation difference at the BG level (P < 0.001). Our results suggest that effacement of the sulcus of the cerebral hemisphere and the loss of contrast at the BG level on brain PMCT indicate the existence of HIE prior to death. PMID:27342771

  5. Paroxetine in Postmortem Fluids and Tissues from Nine Aviation Accident Victims.

    PubMed

    Lewis, Russell J; Kemp, Philip M; Johnson, Robert D

    2015-10-01

    Paroxetine is a selective serotonin reuptake inhibitor commonly prescribed for the treatment of depression, obsessive-compulsive disorder, panic disorder, social anxiety disorder and post-traumatic stress disorder. While the use of paroxetine is considered relatively safe, negative side effects, including nausea, drowsiness, insomnia and dizziness, can adversely affect a pilot's ability to safely operate an aircraft. The use of paroxetine may increase suicidal behavior and suicidal ideation. When relying on postmortem specimens for toxicological evaluation, a general understanding of drug distribution throughout postmortem specimens is important. This laboratory has determined the distribution of paroxetine in postmortem tissues and fluids from nine aviation accident fatalities. Specimens were processed using an n-butyl chloride liquid/liquid extraction followed by gas chromatographic/mass spectrometeric analysis. Blood paroxetine concentrations obtained from these cases ranged from 0.019 to 0.865 µg/mL. The distribution of paroxetine, expressed as mean specimen/blood ratio, was 1.67 ± 1.16 urine (n = 4), 0.08 ± 0.04 vitreous humor (n = 6), 5.77 ± 1.37 liver (n = 8), 9.66 ± 2.58 lung (n = 9), 1.44 ± 0.57 kidney (n = 8), 3.80 ± 0.69 spleen (n = 8), 0.15 ± 0.04 muscle (n = 8), 4.27 ± 2.64 brain (n = 7) and 1.05 ± 0.43 heart (n = 8). The large standard deviations associated with the paroxetine distribution coefficients suggest that paroxetine can experience significant postmortem concentration changes. PMID:26378138

  6. Immunohistoblot analysis on whole human hemispheres from normal and Alzheimer diseased brains.

    PubMed

    Beliczai, Zsuzsa; Varszegi, Szilvia; Gulyas, Balazs; Halldin, Christer; Kasa, Peter; Gulya, Karoly

    2008-12-01

    We demonstrate the feasibility and usefulness of the histoblot immunostaining of cryosections of whole hemispheres of healthy and Alzheimer diseased (AD) human brains by localizing a neuron-specific marker, the anti-neuronal nuclei (NeuN) antigen. As expected, cortical NeuN-immunopositive regions were generally thinner and lighter in the AD brains than in the controls. The advantages of using whole hemisphere histoblots: (1) they provide a low-resolution overview/outline of the antigen distribution in a large surface area, (2) large, thick, and/or unfixed tissue sections from post-mortem samples (perhaps of inferior tissue quality) can be compared, and (3) subsequent immunohistochemistry can be performed on the tissue sections used for the histoblots. PMID:18832000

  7. Evaluation of postmortem S100B levels in the cerebrospinal fluid with regard to the cause of death in medicolegal autopsy.

    PubMed

    Li, Dong-Ri; Michiue, Tomomi; Zhu, Bao-Li; Ishikawa, Takaki; Quan, Li; Zhao, Dong; Yoshida, Chiemi; Chen, Jian-Hua; Wang, Qi; Komatsu, Ayumi; Azuma, Yoko; Maeda, Hitoshi

    2009-04-01

    Previous studies have suggested the usefulness of the postmortem serum S100B level as a marker of the severity of brain damage. In this study, we investigated the S100B level in the cerebrospinal fluid (CSF) in serial autopsy cases (n=216, within 3 days postmortem), including those of blunt injury (n=34: fatal head injury, n=20; others, n=14), sharp instrument injury (n=9), mechanical asphyxiation (n=19), drowning (n=11), fire fatality (n=26), intoxication (n=20), hypothermia (cold exposure, n=16), hyperthermia (heat stroke, n=9), acute cardiac death (n=52) and pneumonia (n=20). The CSF S100B level showed a moderate postmortem time-dependent increase for acute cardiac death (r=0.58, p<0.0001) and asphyxia (r=0.741, p<0.001). In cases of survival time within 48 h, drowning and hypothermia usually showed a lower CSF S100B level (around 500 ng/ml), and the level was higher for delayed head injury death, asphyxia, intoxication, and hyperthermia (around 1500 ng/ml) (p<0.05). In fatal head injury cases, however, CSF S100B did not correlate with the survival time or postmortem interval. A CSF S100B level of >2000 ng/ml in the early postmortem period might be considered a biochemical sign of fatally severe brain damage. PMID:19366640

  8. 14. VIEW IN THE WEST OPERATING GALLERY OF POSTMORTEM CELL ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    14. VIEW IN THE WEST OPERATING GALLERY OF POST-MORTEM CELL WORK STATION AND MANIPULATOR ARMS. - Nevada Test Site, Engine Maintenance Assembly & Disassembly Facility, Area 25, Jackass Flats, Mercury, Nye County, NV

  9. 9 CFR 352.11 - Post-mortem inspection.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ...-mortem inspection. (a) Post-mortem inspection of reindeer, elk, deer, antelope, bison and water buffalo shall be conducted in accordance with the provisions contained in 9 CFR part 310 or as determined by...

  10. 9 CFR 352.11 - Post-mortem inspection.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ...-mortem inspection. (a) Post-mortem inspection of reindeer, elk, deer, antelope, bison and water buffalo shall be conducted in accordance with the provisions contained in 9 CFR part 310 or as determined by...

  11. 9 CFR 352.11 - Post-mortem inspection.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ...-mortem inspection. (a) Post-mortem inspection of reindeer, elk, deer, antelope, bison and water buffalo shall be conducted in accordance with the provisions contained in 9 CFR part 310 or as determined by...

  12. 9 CFR 352.11 - Post-mortem inspection.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ...-mortem inspection. (a) Post-mortem inspection of reindeer, elk, deer, antelope, bison and water buffalo shall be conducted in accordance with the provisions contained in 9 CFR part 310 or as determined by...

  13. 9 CFR 352.11 - Post-mortem inspection.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ...-mortem inspection. (a) Post-mortem inspection of reindeer, elk, deer, antelope, bison and water buffalo shall be conducted in accordance with the provisions contained in 9 CFR part 310 or as determined by...

  14. New pitfalls of high-density postmortem computed tomography.

    PubMed

    Kanazawa, Ayumi; Hyodoh, Hideki; Watanabe, Satoshi; Fukuda, Marika; Baba, Miho; Okazaki, Shunichiro; Mizuo, Keisuke; Hayashi, Etsuko; Inoue, Hiromasa

    2014-09-01

    An 80-year-old female was transferred to the hospital due to a traffic accident. Multiple cranial bone fractures with intracranial hemorrhage and intracranial air were detected. Despite treatment, the patient died after 6h. Twenty-one hours after the patient died, her whole body was scanned by postmortem CT, and a region of high density was detected within the left putamen. The autopsy revealed a cerebral contusion and multiple skull base fractures. Moreover, superabsorbent polymers (SAPs) were found within the left lateral ventricle and adjacent to the putamen, which appeared as a high-density lesion on postmortem CT at the left putamen, where the SAPs were compacted. Both ante- and postmortem conditions should be considered to prevent misdiagnoses based only on postmortem CT. PMID:24916862

  15. 3-D Cytoarchitectonic parcellation of human orbitofrontal cortex. Correlation with postmortem MRI

    PubMed Central

    Uylings, Harry B.M.; Sanz-Arigita, Ernesto J.; de Vos, Koos; Pool, Chris W.; Evers, Paul; Rajkowska, Grazyna

    2010-01-01

    The orbitofrontal cortex (OFC) is located on the basal surface of the frontal lobe and is distinguished by its unique anatomical and functional features. Clinical and postmortem studies suggest the involvement of the orbitofrontal cortex in psychiatric disorders. However, the exact parcellation of this cortical region is still a matter of debate. Therefore, the goal of this study is to provide a detailed description of the extent of borders of individual orbitofrontal cortical areas using cytoarchitectonic criteria in a large sample of human brains, which could be applied by independent neuroanatomists. To make this microscopic parcellation useful to neuroimaging studies, magnetic resonance images of postmortem brains in the coronal plane were collected prior to the preparation of coronal histological sections from the same brains. A complete series of coronal sections from 6 normal human brains and partial sections from the frontal cortex of 21 normal human brains were stained with general histological and immunohistochemical methods specific for different cell-types, These sections were examined microscopically by two independent neuroanatomists (HBMU and GR) to achieve reproducible delineations. After the borders were determined, the tissue sections were superimposed on corresponding MR images. Based on our cytoarchitectonical criteria, Brodmann's areas 47 and 11 were included in the human orbitofrontal cortex. Area 47 was further subdivided into three medial (located on the medial, anterior and posterior orbital gyri) and two lateral (located on the lateral orbital gyrus) subareas. In addition, we observed an anterior-posterior gradient in the cytoarchitecture of areas 11 and 47. The transverse orbital sulcus corresponds roughly to the transition between the subregions of the anterior and posterior OFC. Finally, the present delineation is contrasted with an overview of the different published nomenclatures for the OFC parcellation. PMID:20538437

  16. Distribution of ether in two postmortem cases.

    PubMed

    Cox, Dawn; DeRienz, Rebecca; Jufer Phipps, Rebecca A; Levine, Barry; Jacobs, Aaron; Fowler, David

    2006-10-01

    Diethyl ether (ether) is a volatile liquid that was used in the 1800s as an anesthetic agent; however, it is no longer used for this purpose, partly because of its odor and flammability. Two postmortem cases in which ether was detected are presented. The first case was an 18-year-old male found hanging from a basement ceiling brace in a semi-sitting position with a gas mask covering his face. A container of Prestone starting fluid and a bong were found on the floor close to the body. The second case was a 20-year-old male found unresponsive in his dormitory room with two black plastic trash bags secured over his head. Two saturated rags and a resealable bag containing a clear liquid were contained within these trash bags. An almost empty can of Tradco starting fluid was also found at the scene. Ether concentrations were determined by headspace gas chromatography-mass spectrometry in the selective ion monitoring mode. In case #1, the medical examiner ruled that the cause of death was asphyxia due to hanging; the manner of death was undetermined. In case #2, the medical examiner ruled that the cause of death was asphyxia and the manner of death was suicide. PMID:17132265

  17. Coronary atherosclerosis -- a postmortem histopathological study.

    PubMed

    Kumar, S; Kumar, Verma A; Kumar, N; Baranwal, R K; Kumar, Verma R; Singh, M

    2012-01-01

    Cardiovascular disease in general and coronary heart disease in particular remains the leading cause of morbidity and mortality in developed countries. The aim of this study was to look at the prevalence of coronary atherosclerosis, its severity and site of involvement in postmortem hearts. The hearts of 30-60 yrs old, fifty dead victims were considered who died from various natural and unnatural deaths. After autopsy, coronary arteries were inspected grossly and microscopically. Out of all these cases, 10 cases (20 %) showed no pathological lesions. Total distribution of lesions in the coronaries are as follows; 34 (68 %) atheromatous lesions in Left Anterior Descending Artery, 25 (50 %) lesions in the Right Coronary Artery, 18 (36 %) lesions in Left Circumflex. Proximal involvement was more common except in the right coronary artery, which was involved distally. The overall prevalence of coronary atherosclerosis in the present study was comparable with that noted by other investigators in autopsy studied. There is a higher prevalence of atherosclerosis in Indians, which may be due to changes in life-styles and other risks factors (Tab. 1, Ref. 14). Full Text in PDF www.elis.sk. PMID:22502752

  18. Value Added?

    ERIC Educational Resources Information Center

    UCLA IDEA, 2012

    2012-01-01

    Value added measures (VAM) uses changes in student test scores to determine how much "value" an individual teacher has "added" to student growth during the school year. Some policymakers, school districts, and educational advocates have applauded VAM as a straightforward measure of teacher effectiveness: the better a teacher, the better students…

  19. What can post-mortem studies tell us about the pathoetiology of suicide?

    PubMed Central

    Pandey, Ghanshyam N; Dwivedi, Yogesh

    2011-01-01

    Suicide is a major public health concern; however, its neurobiology is unclear. Post-mortem brain tissue obtained from suicide victims and normal controls offers a useful method for studying the neurobiology of suicide. Despite several limitations, these studies have offered important leads in the neurobiology of suicide. In this article, we discuss some important findings resulting from these studies, focusing on serotonergic mechanisms, signal transduction systems, neuroendocrine studies and immune function abnormalities in suicide. These studies suggest that abnormalities of certain receptor subtypes, components of signaling systems such as protein kinase C and protein kinase A, transcription factors such as cyclic AMP response element-binding protein and neurotrophins may play an important role in the pathophysiology of suicide. These studies also suggest abnormalities of hypothalamic–pituitary–adrenal axis system components, feedback mechanisms and cytokines, which are chemical mediators of the immune functions. Post-mortem brain tissue offers an opportunity for future studies, such as genetic and epigenetic studies. PMID:21436961

  20. Wide-ranging alterations in the brain fatty acid complement of subjects with late Alzheimer’s disease as detected by GC-MS

    PubMed Central

    Nasaruddin, Muhammad Luqman; Hölscher, Christian; Kehoe, Patrick; Graham, Stewart Francis; Green, Brian Desmond

    2016-01-01

    Disturbed lipid metabolism is a well-established feature of human Alzheimer’s disease (AD). The present study used gas chromatography-mass spectrometry (GC-MS) analysis of fatty acid methyl esters (FAMES) to profile all detectable fatty acid (FA) species present in post-mortem neocortical tissue (Brodmann 7 region). Quantitative targeted analysis was undertaken from 29 subjects (n=15 age-matched controls; n=14 late-stage AD). GC-MS analysis of FAMES detected a total of 24 FAs and of these, 20 were fully quantifiable. The results showed significant and wide ranging elevations in AD brain FA concentrations. A total of 9 FAs were elevated in AD with cis-13,16-docosenoic acid increased most (170%; P=0.033). Intriguingly, docosahexanoic acid (DHA; C22:6) concentrations were elevated (47%; P=0.018) which conflicts with the findings of others (unaltered or decreased) in some brain regions after the onset of AD. Furthermore, our results appear to indicate that subject gender influences brain FA levels in AD subjects (but not in age-matched control subjects). Among AD subjects 7 FA species were significantly higher in males than in females. These preliminary findings pinpoint FA disturbances as potentially important in the pathology of AD. Further work is required to determine if such changes are influenced by disease severity or different types of dementia. PMID:27069549

  1. Wide-ranging alterations in the brain fatty acid complement of subjects with late Alzheimer's disease as detected by GC-MS.

    PubMed

    Nasaruddin, Muhammad Luqman; Hölscher, Christian; Kehoe, Patrick; Graham, Stewart Francis; Green, Brian Desmond

    2016-01-01

    Disturbed lipid metabolism is a well-established feature of human Alzheimer's disease (AD). The present study used gas chromatography-mass spectrometry (GC-MS) analysis of fatty acid methyl esters (FAMES) to profile all detectable fatty acid (FA) species present in post-mortem neocortical tissue (Brodmann 7 region). Quantitative targeted analysis was undertaken from 29 subjects (n=15 age-matched controls; n=14 late-stage AD). GC-MS analysis of FAMES detected a total of 24 FAs and of these, 20 were fully quantifiable. The results showed significant and wide ranging elevations in AD brain FA concentrations. A total of 9 FAs were elevated in AD with cis-13,16-docosenoic acid increased most (170%; P=0.033). Intriguingly, docosahexanoic acid (DHA; C22:6) concentrations were elevated (47%; P=0.018) which conflicts with the findings of others (unaltered or decreased) in some brain regions after the onset of AD. Furthermore, our results appear to indicate that subject gender influences brain FA levels in AD subjects (but not in age-matched control subjects). Among AD subjects 7 FA species were significantly higher in males than in females. These preliminary findings pinpoint FA disturbances as potentially important in the pathology of AD. Further work is required to determine if such changes are influenced by disease severity or different types of dementia. PMID:27069549

  2. Neuronal uptake and propagation of a rare phosphorylated high-molecular-weight tau derived from Alzheimer's disease brain

    PubMed Central

    Takeda, Shuko; Wegmann, Susanne; Cho, Hansang; DeVos, Sarah L.; Commins, Caitlin; Roe, Allyson D.; Nicholls, Samantha B.; Carlson, George A.; Pitstick, Rose; Nobuhara, Chloe K.; Costantino, Isabel; Frosch, Matthew P.; Müller, Daniel J.; Irimia, Daniel; Hyman, Bradley T.

    2015-01-01

    Tau pathology is known to spread in a hierarchical pattern in Alzheimer's disease (AD) brain during disease progression, likely by trans-synaptic tau transfer between neurons. However, the tau species involved in inter-neuron propagation remains unclear. To identify tau species responsible for propagation, we examined uptake and propagation properties of different tau species derived from postmortem cortical extracts and brain interstitial fluid of tau-transgenic mice, as well as human AD cortices. Here we show that PBS-soluble phosphorylated high-molecular-weight (HMW) tau, though very low in abundance, is taken up, axonally transported, and passed on to synaptically connected neurons. Our findings suggest that a rare species of soluble phosphorylated HMW tau is the endogenous form of tau involved in propagation and could be a target for therapeutic intervention and biomarker development. PMID:26458742

  3. Amyloid Triggers Extensive Cerebral Angiogenesis Causing Blood Brain Barrier Permeability and Hypervascularity in Alzheimer's Disease

    PubMed Central

    Biron, Kaan E.; Dickstein, Dara L.; Gopaul, Rayshad; Jefferies, Wilfred A.

    2011-01-01

    Evidence of reduced blood-brain barrier (BBB) integrity preceding other Alzheimer's disease (AD) pathology provides a strong link between cerebrovascular angiopathy and AD. However, the “Vascular hypothesis”, holds that BBB leakiness in AD is likely due to hypoxia and neuroinflammation leading to vascular deterioration and apoptosis. We propose an alternative hypothesis: amyloidogenesis promotes extensive neoangiogenesis leading to increased vascular permeability and subsequent hypervascularization in AD. Cerebrovascular integrity was characterized in Tg2576 AD model mice that overexpress the human amyloid precursor protein (APP) containing the double missense mutations, APPsw, found in a Swedish family, that causes early-onset AD. The expression of tight junction (TJ) proteins, occludin and ZO-1, were examined in conjunction with markers of apoptosis and angiogenesis. In aged Tg2576 AD mice, a significant increase in the incidence of disrupted TJs, compared to age matched wild-type littermates and young mice of both genotypes, was directly linked to an increased microvascular density but not apoptosis, which strongly supports amyloidogenic triggered hypervascularity as the basis for BBB disruption. Hypervascularity in human patients was corroborated in a comparison of postmortem brain tissues from AD and controls. Our results demonstrate that amylodogenesis mediates BBB disruption and leakiness through promoting neoangiogenesis and hypervascularity, resulting in the redistribution of TJs that maintain the barrier and thus, provides a new paradigm for integrating vascular remodeling with the pathophysiology observed in AD. Thus the extensive angiogenesis identified in AD brain, exhibits parallels to the neovascularity evident in the pathophysiology of other diseases such as age-related macular degeneration. PMID:21909359

  4. Volumetric analysis of the diagonal band of Broca in patients with schizophrenia and affective disorders: A post-mortem study.

    PubMed

    Brisch, Ralf; Bernstein, Hans-Gert; Dobrowolny, Henrik; Krzyżanowska, Marta; Jankowski, Zbigniew; Bogerts, Bernhard; Gos, Tomasz

    2016-05-01

    The human diagonal band of Broca is connected to other parts of the limbic system, such as the hippocampus, that are involved in the pathology of schizophrenia. This study aimed to characterize the volume and anterior-to-posterior distance of the human diagonal band of Broca (vertical limb) from post-mortem brains obtained from three groups: healthy control subjects (N = 17), patients with schizophrenia (N = 26), and patients with affective disorders (N = 12). There were no significant differences in the volume or anterior-to-posterior distance in the patients with schizophrenia or affective disorders compared with the healthy control subjects. To date, this is the first post-mortem investigation measuring the volume and the anterior-to-posterior distance of the diagonal band of Broca (vertical limb) in patients with schizophrenia or affective disorders compared with healthy control subjects. Clin. Anat. 29:466-472, 2016. © 2015 Wiley Periodicals, Inc. PMID:26457806

  5. A combined post-mortem magnetic resonance imaging and quantitative histological study of multiple sclerosis pathology

    PubMed Central

    Kolasinski, James; Chance, Steven A.; DeLuca, Gabriele C.; Esiri, Margaret M.; Chang, Eun-Hyuk; Palace, Jacqueline A.; McNab, Jennifer A.; Jenkinson, Mark; Miller, Karla L.; Johansen-Berg, Heidi

    2012-01-01

    Multiple sclerosis is a chronic inflammatory neurological condition characterized by focal and diffuse neurodegeneration and demyelination throughout the central nervous system. Factors influencing the progression of pathology are poorly understood. One hypothesis is that anatomical connectivity influences the spread of neurodegeneration. This predicts that measures of neurodegeneration will correlate most strongly between interconnected structures. However, such patterns have been difficult to quantify through post-mortem neuropathology or in vivo scanning alone. In this study, we used the complementary approaches of whole brain post-mortem magnetic resonance imaging and quantitative histology to assess patterns of multiple sclerosis pathology. Two thalamo-cortical projection systems were considered based on their distinct neuroanatomy and their documented involvement in multiple sclerosis: lateral geniculate nucleus to primary visual cortex and mediodorsal nucleus of the thalamus to prefrontal cortex. Within the anatomically distinct thalamo-cortical projection systems, magnetic resonance imaging derived cortical thickness was correlated significantly with both a measure of myelination in the connected tract and a measure of connected thalamic nucleus cell density. Such correlations did not exist between these markers of neurodegeneration across different thalamo-cortical systems. Magnetic resonance imaging lesion analysis depicted clearly demarcated subcortical lesions impinging on the white matter tracts of interest; however, quantitation of the extent of lesion-tract overlap failed to demonstrate any appreciable association with the severity of markers of diffuse pathology within each thalamo-cortical projection system. Diffusion-weighted magnetic resonance imaging metrics in both white matter tracts were correlated significantly with a histologically derived measure of tract myelination. These data demonstrate for the first time the relevance of functional

  6. Post-mortem CT and MRI: appropriate post-mortem imaging appearances and changes related to cardiopulmonary resuscitation.

    PubMed

    Offiah, Curtis E; Dean, Jonathan

    2016-01-01

    Post-mortem cross-sectional imaging in the form of CT and, less frequently, MRI is an emerging facility in the evaluation of cause-of-death and human identification for the coronial service as well as in assisting the forensic investigation of suspicious deaths and homicide. There are marked differences between the radiological evaluation and interpretation of the CT and MRI features of the live patient (i.e. antemortem imaging) and the evaluation and interpretation of post-mortem CT and MRI appearances. In addition to the absence of frequently utilized tissue enhancement following intravenous contrast administration in antemortem imaging, there are a number of variable changes which occur in the tissues and organs of the body as a normal process following death, some of which are, in addition, affected significantly by environmental factors. Many patients and victims will also have undergone aggressive attempts at cardiopulmonary resuscitation in the perimortem period which will also significantly alter post-mortem CT and MRI appearances. It is paramount that the radiologist and pathologist engaged in the interpretation of such post-mortem imaging are familiar with the appropriate non-pathological imaging changes germane to death, the post-mortem interval and cardiopulmonary resuscitation in order to avoid erroneously attributing such changes to trauma or pathology. Some of the more frequently encountered radiological imaging considerations of this nature will be reviewed. PMID:26562099

  7. Adding Value.

    ERIC Educational Resources Information Center

    Orsini, Larry L.; Hudack, Lawrence R.; Zekan, Donald L.

    1999-01-01

    The value-added statement (VAS), relatively unknown in the United States, is used in financial reports by many European companies. Saint Bonaventure University (New York) has adapted a VAS to make it appropriate for not-for-profit universities by identifying stakeholder groups (students, faculty, administrators/support personnel, creditors, the…

  8. A case of acute subdural hematoma due to ruptured aneurysm detected by postmortem angiography.

    PubMed

    Inokuchi, Go; Makino, Yohsuke; Yajima, Daisuke; Motomura, Ayumi; Chiba, Fumiko; Torimitsu, Suguru; Hoshioka, Yumi; Iwase, Hirotaro

    2016-03-01

    Acute subdural hematoma (ASDH) is mostly caused by head trauma, but intrinsic causes also exist such as aneurysm rupture. We describe here a case involving a man in his 70s who was found lying on the bedroom floor by his family. CT performed at the hospital showed ASDH and a forensic autopsy was requested. Postmortem cerebral angiography showed dilatation of the bifurcation of the middle cerebral artery, which coincided with the dilated part of the Sylvian fissure. Extravasation of contrast medium into the subdural hematoma from this site was suggestive of a ruptured aneurysm. Autopsy revealed a fleshy hematoma (total weight 110 g) in the right subdural space and findings of brain herniation. As indicated on angiography, a ruptured saccular aneurysm was confirmed at the bifurcation of the middle cerebral artery. Obvious injuries to the head or face could not be detected on either external or internal examination, and intrinsic ASDH due to a ruptured middle cerebral artery aneurysm was determined as the cause of death. One of the key points of forensic diagnosis is the strict differentiation between intrinsic and extrinsic onset for conditions leading to death. Although most subdural hematomas (SDH) are caused by extrinsic factors, forensic pathologists should consider the possibility of intrinsic SDH. In addition, postmortem angiography can be useful for identifying vascular lesions in such cases. PMID:26362305

  9. Search for fungi-specific metabolites of four model drugs in postmortem blood as potential indicators of postmortem fungal metabolism.

    PubMed

    Martínez-Ramírez, Jorge A; Strien, Juliane; Walther, Grit; Peters, Frank T

    2016-05-01

    Fungi colonizing cadavers are capable of drug metabolism and may thus change the metabolite pattern or concentration of drugs in forensic postmortem samples. The purpose of this study was to check for the presence of such changes by searching fungi-specific metabolites of four model drugs (amitriptyline, metoprolol, mirtazapine, and zolpidem) in decomposed postmortem blood samples from 33 cases involving these drugs. After isolation and identification of fungal strains present in the samples, each isolate was incubated in Sabouraud medium at 25°C for up to 120h with each model drug. One part of the supernatants was directly analyzed by liquid chromatography-tandem mass spectrometry (LC-MS/MS), another after liquid-liquid extraction with chlorobutane and concentration. From 21 out of 33 decomposed postmortem blood samples (64%) a total of 30 different strains could be isolated, one from the class of Ascomycete and the rest belonging to 15 species from 8 different genera (number of species): Aspergillus (2), Botrytis (1), Candida (8), Fusarium (1), Mucor (1), Penicillium (1), and Rodothorula (1). In the in vitro studies, these microorganisms were found capable of N-demethylation and N-oxidation of amitriptyline and mirtazapine, O-demethylation followed by side chain oxidation of metoprolol as well as hydroxylation of all four-model drugs. In two of the postmortem blood samples, from which the fungi Aspergillus jensenii, Candida parapsilosis. and Mucor circinelloides had been isolated, a fungi-specific hydroxy zolpidem metabolite was detected. The presence of this metabolite in postmortem samples likely indicates postmortem fungal biodegradation. PMID:27022860

  10. DIS in AdS

    NASA Astrophysics Data System (ADS)

    Albacete, Javier L.; Kovchegov, Yuri V.; Taliotis, Anastasios

    2009-03-01

    We calculate the total cross section for the scattering of a quark-anti-quark dipole on a large nucleus at high energy for a strongly coupled N = 4 super Yang-Mills theory using AdS/CFT correspondence. We model the nucleus by a metric of a shock wave in AdS5. We then calculate the expectation value of the Wilson loop (the dipole) by finding the extrema of the Nambu-Goto action for an open string attached to the quark and antiquark lines of the loop in the background of an AdS5 shock wave. We find two physically meaningful extremal string configurations. For both solutions we obtain the forward scattering amplitude N for the quark dipole-nucleus scattering. We study the onset of unitarity with increasing center-of-mass energy and transverse size of the dipole: we observe that for both solutions the saturation scale Qs is independent of energy/Bjorken-x and depends on the atomic number of the nucleus as Qs˜A1/3. Finally we observe that while one of the solutions we found corresponds to the pomeron intercept of αP = 2 found earlier in the literature, when extended to higher energy or larger dipole sizes it violates the black disk limit. The other solution we found respects the black disk limit and yields the pomeron intercept of αP = 1.5. We thus conjecture that the right pomeron intercept in gauge theories at strong coupling may be αP = 1.5.

  11. microRNA (miRNA) speciation in Alzheimer's disease (AD) cerebrospinal fluid (CSF) and extracellular fluid (ECF).

    PubMed

    Alexandrov, Peter N; Dua, Prerna; Hill, James M; Bhattacharjee, Surjyadipta; Zhao, Yuhai; Lukiw, Walter J

    2012-01-01

    Human cerebrospinal fluid (CSF), produced by the choroid plexus and secreted into the brain ventricles and subarachnoid space, plays critical roles in intra-cerebral transport and the biophysical and immune protection of the brain. CSF composition provides valuable insight into soluble pathogenic bio-markers that may be diagnostic for brain disease. In these experiments we analyzed amyloid beta (Aβ) peptide and micro RNA (miRNA) abundance in CSF and in short post-mortem interval (PMI <2.1 hr) brain tissue-derived extracellular fluid (ECF) from Alzheimer's disease (AD) and age-matched control neocortex. There was a trend for decreased abundance of Aβ42 in the CSF and ECF in AD but it did not reach statistical significance (mean age ~72 yr; N=12; p~0.06, ANOVA). The most abundant nucleic acids in AD CSF and ECF were miRNAs, and their speciation and inducibility were studied further. Fluorescent miRNA-array-based analysis indicated significant increases in miRNA-9, miRNA-125b, miRNA-146a, miRNA-155 in AD CSF and ECF (N=12; p<0.01, ANOVA). Primary human neuronal-glial (HNG) cell co-cultures stressed with AD-derived ECF also displayed an up-regulation of these miRNAs, an effect that was quenched using the anti-NF-кB agents caffeic acid phenethyl ester (CAPE) or 1-fluoro-2-[2-(4-methoxy-phenyl)-ethenyl]-benzene (CAY10512). Increases in miRNAs were confirmed independently using a highly sensitive LED-Northern dot-blot assay. Several of these NF-кB-sensitive miRNAs are known to be up-regulated in AD brain, and associate with the progressive spreading of inflammatory neurodegeneration. The results indicate that miRNA-9, miRNA-125b, miRNA-146a and miRNA-155 are CSF- and ECF-abundant, NF-кB-sensitive pro-inflammatory miRNAs, and their enrichment in circulating CSF and ECF suggest that they may be involved in the modulation or proliferation of miRNA-triggered pathogenic signaling throughout the brain and central nervous system (CNS). PMID:23301201

  12. Controlled Cortical Impact Traumatic Brain Injury in 3xTg-AD Mice Causes Acute Intra-axonal Amyloid-beta Accumulation and Independently Accelerates the Development of Tau Abnormalities

    PubMed Central

    Tran, Hien T; LaFerla, Frank M.; Holtzman, David M.; Brody, David L.

    2011-01-01

    Alzheimer’s disease (AD) is a neurodegenerative disorder characterized pathologically by progressive neuronal loss, extracellular plaques containing the amyloid-β (Aβ) peptides, and neurofibrillary tangles composed of hyperphosphorylated tau proteins. Aβ is thought to act upstream of tau, affecting its phosphorylation and therefore aggregation state. One of the major risk factors for AD is traumatic brain injury (TBI). Acute intra-axonal Aβ and diffuse extracellular plaques occur in approximately 30% of human subjects following severe TBI. Intra-axonal accumulations of tau but not tangle-like pathologies have also been found in these patients. Whether and how these acute accumulations contribute to subsequent AD development is not known, and the interaction between Aβ and tau in the setting of TBI has not been investigated. Here, we report that controlled cortical impact TBI in 3xTg-AD mice resulted in intra-axonal Aβ accumulations and increased phospho-tau immunoreactivity at 24 hours and up to 7 days post TBI. Given these findings, we investigated the relationship between Aβ and tau pathologies following trauma in this model by systemic treatment of Compound E to inhibit γ-secrectase activity, a proteolytic process required for Aβ production. Compound E treatment successfully blocked post-traumatic Aβ accumulation in these injured mice at both time points. However, tau pathology was not affected. Our data support a causal role for TBI in acceleration of AD-related pathologies, and suggest that TBI may independently affect Aβ and tau abnormalities. Future studies will be required to assess the behavioral and long-term neurodegenerative consequences of these pathologies. PMID:21715616

  13. 18. Photocopy of photograph. VIEW WITHIN POSTMORTEM CELL OF MANIPULATOR ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    18. Photocopy of photograph. VIEW WITHIN POST-MORTEM CELL OF MANIPULATOR ARMS BEING USED TO MOVE METAL BARS FROM ONE LOCATION TO ANOTHER. Photographer unknown, ca. 1965, original photograph and negative on file at the Remote Sensing Laboratory, Department of Energy, Nevada Operations Office. - Nevada Test Site, Engine Maintenance Assembly & Disassembly Facility, Area 25, Jackass Flats, Mercury, Nye County, NV

  14. 13. VIEW OF EAST OPERATING GALLERY ALONG THE POSTMORTEM CELLS. ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    13. VIEW OF EAST OPERATING GALLERY ALONG THE POST-MORTEM CELLS. A NUMBER OF MANIPULATOR ARMS COVERED WITH PLASTIC ARE ON THE LEFT WALL. - Nevada Test Site, Engine Maintenance Assembly & Disassembly Facility, Area 25, Jackass Flats, Mercury, Nye County, NV

  15. Advances in post-mortem CT-angiography

    PubMed Central

    Grimm, J; Dominguez, A; Vanhaebost, J; Mangin, P

    2014-01-01

    Performing a post-mortem multidetector CT (MDCT) scan has already become routine in some institutes of forensic medicine. To better visualize the vascular system, different techniques of post-mortem CT-angiography have been explored, which can essentially be divided into partial- and whole-body angiography techniques. Probably the most frequently applied technique today is the so-called multiphase post-mortem CT-angiography (MPMCTA) a standardized method for investigating the vessels of the head, thorax and abdomen. Different studies exist, describing its use for medicolegal investigations, and its advantages as well as its artefacts and pitfalls. With the aim to investigate the performance of PMCTA and to develop and validate techniques, an international working group was created in 2012 called the “Technical Working Group Post-mortem Angiography Methods” (TWGPAM). Beyond its primary perspective, the goals of this group include creating recommendations for the indication of the investigation and for the interpretation of the images and to distribute knowledge about PMCTA. This article provides an overview about the different approaches that have been developed and tested in recent years and an update about ongoing research in this field. It will explain the technique of MPMCTA in detail and give an outline of its indications, application, advantages and limitations. PMID:24234582

  16. Sarcomere length influences postmortem proteolysis of excised bovine semitendinosus muscle

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The interaction between sarcomere length and postmortem proteolysis as related to meat tenderness is not clear. The extent of thick and thin filament overlap alters actomyosin binding and may alter substrate availability during aging-induced tenderization. The objective of this study was to determin...

  17. Interpretation of postmortem vitreous concentrations of sodium and chloride.

    PubMed

    Zilg, B; Alkass, K; Berg, S; Druid, H

    2016-06-01

    Vitreous fluid can be used to analyze sodium and chloride levels in deceased persons, but it remains unclear to what extent such results can be used to diagnose antemortem sodium or chloride imbalances. In this study we present vitreous sodium and chloride levels from more than 3000 cases. We show that vitreous sodium and chloride levels both decrease with approximately 2.2mmol/L per day after death. Since potassium is a well-established marker for postmortem interval (PMI) and easily can be analyzed along with sodium and chloride, we have correlated sodium and chloride levels with the potassium levels and present postmortem reference ranges relative the potassium levels. We found that virtually all cases outside the reference range show signs of antemortem hypo- or hypernatremia. Vitreous sodium or chloride levels can be the only means to diagnose cases of water or salt intoxication, beer potomania or dehydration. We further show that postmortem vitreous sodium and chloride strongly correlate and in practice can be used interchangeably if analysis of one of the ions fails. It has been suggested that vitreous sodium and chloride levels can be used to diagnose drowning or to distinguish saltwater from freshwater drowning. Our results show that in cases of freshwater drowning, vitreous sodium levels are decreased, but that this mainly is an effect of postmortem diffusion between the eye and surrounding water rather than due to the drowning process, since the decrease in sodium levels correlates with immersion time. PMID:27105154

  18. Association of Brain DNA Methylation in SORL1, ABCA7, HLA-DRB5, SLC24A4, and BIN1 With Pathological Diagnosis of Alzheimer Disease

    PubMed Central

    Yu, Lei; Chibnik, Lori B.; Srivastava, Gyan P.; Pochet, Nathalie; Yang, Jingyun; Xu, Jishu; Kozubek, James; Obholzer, Nikolaus; Leurgans, Sue E.; Schneider, Julie A.; Meissner, Alexander; De Jager, Philip L.; Bennett, David A.

    2015-01-01

    IMPORTANCE Recent large-scale genome-wide association studies have discovered several genetic variants associated with Alzheimer disease (AD); however, the extent to which DNA methylation in these AD loci contributes to the disease susceptibility remains unknown. OBJECTIVE To examine the association of brain DNA methylation in 28 reported AD loci with AD pathologies. DESIGN, SETTING, AND PARTICIPANTS Ongoing community-based clinical pathological cohort studies of aging and dementia (the Religious Orders Study and the Rush Memory and Aging Project) among 740 autopsied participants 66.0 to 108.3 years old. EXPOSURES DNA methylation levels at individual CpG sites generated from dorsolateral prefrontal cortex tissue using a bead assay. MAIN OUTCOMES AND MEASURES Pathological diagnosis of AD by National Institute on Aging–Reagan criteria following a standard postmortem examination. RESULTS Overall, 447 participants (60.4%) met the criteria for pathological diagnosis of AD. Brain DNA methylation in SORL1, ABCA7, HLA-DRB5, SLC24A4, and BIN1 was associated with pathological AD. The association was robustly retained after replacing the binary trait of pathological AD with 2 quantitative and molecular specific hallmarks of AD, namely, Aβ load and paired helical filament tau tangle density. Furthermore, RNA expression of transcripts of SORL1 and ABCA7 was associated with paired helical filament tau tangle density, and the expression of BIN1 was associated with Aβ load. CONCLUSIONS AND RELEVANCE Brain DNA methylation in multiple AD loci is associated with AD pathologies. The results provide further evidence that disruption of DNA methylation is involved in the pathological process of AD. PMID:25365775

  19. TECHNICAL BRIEF: Isolation of total DNA from postmortem human eye tissues and quality comparison between iris and retina

    PubMed Central

    Wang, Jay Ching Chieh; Wang, Aikun; Gao, Jiangyuan; Cao, Sijia; Samad, Idris; Zhang, Dean; Ritland, Carol; Cui, Jing Z.

    2012-01-01

    Background Recent genomic technologies have propelled our understanding of the mechanisms underlying complex eye diseases such as age-related macular degeneration (AMD). Genotyping postmortem eye tissues for known single nucleotide polymorphisms (SNPs) associated with AMD may prove valuable, especially when combined with information obtained through other methods such as immunohistochemistry, western blot, enzyme-linked immunosorbent assay (ELISA), and proteomics. Initially intending to genotype postmortem eye tissues for AMD-related SNPs, our group became interested in isolating and comparing the quality of DNA from the iris and retina of postmortem donor eyes. Since there is no previously published protocol in the literature on this topic, we present a protocol suitable for isolating high-quality DNA from postmortem eye tissues for genomic studies. Methods DNA from 33 retinal samples and 35 iris samples was extracted using the phenol-chloroform-isoamyl method from postmortem donor eye tissues. The quantity of DNA was measured with a spectrophotometer while the quality was checked using gel electrophoresis. The DNA samples were then amplified with PCR for the complement factor H (CFH) gene. The purified amplified products were then genotyped for the SNPs in the CFH gene. Results Regarding concentration, the retina yielded 936 ng/μl of DNA, while the iris yielded 78 ng/μl of DNA. Retinal DNA was also purer than iris DNA (260/280=1.78 vs. 1.46, respectively), and produced superior PCR results. Retinal tissue yielded significantly more DNA than the iris tissue per mg of sample (21.7 ng/μl/mg vs. 7.42 ng/μl/mg). Retinal DNA can be readily amplified with PCR, while iris DNA can also be amplified by adding bovine serum albumin. Overall, retinal tissues yielded DNA of superior quality, quantity, and suitability for genotyping and genomic studies. Conclusions The protocol presented here provides a clear and reliable method for isolating total DNA from postmortem eye

  20. Postmortem findings in the Nijmegen breakage syndrome.

    PubMed

    Van de Kaa, C A; Weemaes, C M; Wesseling, P; Schaafsma, H E; Haraldsson, A; De Weger, R A

    1994-01-01

    Autopsy findings for two patients with the Nijmegen breakage syndrome (NBS) are presented. This syndrome has the same type of immunologic and cytogenetic abnormalities as ataxia telangiectasia (AT). In NBS, however, microcephaly is found and progressive cerebellar ataxia and oculocutaneous telangiectasia are lacking. We demonstrate a clear neuropathologic difference between these two syndromes, as the diffuse cortical cerebellar degeneration characteristic of AT was absent in NBS. In the thymus the histologic picture was suggestive of simple dysplasia. Lymphoid tissues were slightly atrophic but otherwise structurally normal. In one of the two presented cases an extranodal diffuse large cell malignant non-Hodgkin lymphoma of B cell immunoblastic type was found in Waldeyer's ring, in the small and large intestines, and in the brain, whose sequelae had caused death. Six of the 19 patients known with certainty to have this syndrome have developed lymphoid malignancy, which indicates that these patients are prone to develop malignancies. PMID:7808977

  1. Histone H3 acetylation in the postmortem Parkinson's disease primary motor cortex.

    PubMed

    Gebremedhin, Kibrom G; Rademacher, David J

    2016-08-01

    Although the role of epigenetics in Parkinson's disease (PD) has not been extensively studied, α-synuclein, the main component of Lewy bodies, decreased histone H3 acetylation. Here, we determined if there were histone acetylation changes in the primary motor cortex which, according to the Braak model, is one of the last brain regions affected in PD. Net histone H3 acetylation, histone H3 lysine 9 (H3K9), histone H3 lysine 14 (H3K14), histone H3 lysine 18 (H3K18), and histone H3 lysine 23 (H3K23) acetylation was assessed in the primary motor cortex of those affected and unaffected by PD. There was net increase in histone H3 acetylation due to increased H3K14 and H3K18 acetylation. There was a decrease in H3K9 acetylation. No between-groups difference was detected in H3K23 acetylation. Relationships between Unified Lewy Body Staging scores and histone H3 acetylation and substantia nigra depigmentation scores and histone H3 acetylation were observed. No relationships were detected between postmortem interval and histone H3 acetylation and expired age and histone H3 acetylation. These correlational data support the notion that the histone H3 acetylation changes observed here are not due to the postmortem interval or aging. Instead, they are due to PD and/or factors that covary with PD. The data suggest enhanced gene transcription in the primary motor cortex of the PD brain due to increase H3K14 and H3K18 acetylation. This effect is partially offset by a decreased H3K9 acetylation, which might repress gene transcription. PMID:27241718

  2. Maturation processes in automatic change detection as revealed by event-related brain potentials and dipole source localization: significance for adult AD/HD.

    PubMed

    Wild-Wall, Nele; Oades, Robert D; Juran, Stephanie A

    2005-10-01

    Mismatch negativity (MMN) is an event-related potential reflecting automatic attention-related information processing marking the detection of auditory change. The bilateral scalp distribution develops by 14 years of age, and is elicited with adult latencies by 17 years. But consistent with reports of continued brain maturation after adolescence, we show here that features of the temporal and frontal lobe dipole sources also continue to develop in the third decade of life. This has consequences for studies of the developmental course of MMN anomalies, from childhood into adulthood, in attention-deficit/hyperactivity disorder. Two groups of healthy subjects with mean ages of 17 and 30 years were presented with a 3-tone auditory oddball. The duration-deviant MMN was recorded during attention to a visual discrimination (auditory-passive condition) and an active auditory discrimination. MMN amplitudes were smaller in the older subjects and the MMN lasted longer over the right hemisphere. Latencies and moments of the four dipoles in the temporal and frontal lobes did not distinguish the two subject-groups. But both temporal lobe sources were located significantly more ventrally and further left in the young adult than in the adolescent subjects. The left cingular source moved posteriorly and the right inferior frontal source moved antero-medially in the older subjects. Brain development in the third decade may cause the two frontal sources to move apart on the rostro-caudal axis but the temporal lobe sources to move left on the lateral and down on the dorsoventral axes. Thus special care is necessary in interpreting putative dysfunctional neurobiological changes in developmental attention-deficit disorders where as-yet-unspecified sub-groups may show a late developmental lag, partial lag, or no lag at all, associated with other impairments. PMID:15922470

  3. DIS in AdS

    SciTech Connect

    Albacete, Javier L.; Kovchegov, Yuri V.; Taliotis, Anastasios

    2009-03-23

    We calculate the total cross section for the scattering of a quark-anti-quark dipole on a large nucleus at high energy for a strongly coupled N = 4 super Yang-Mills theory using AdS/CFT correspondence. We model the nucleus by a metric of a shock wave in AdS{sub 5}. We then calculate the expectation value of the Wilson loop (the dipole) by finding the extrema of the Nambu-Goto action for an open string attached to the quark and antiquark lines of the loop in the background of an AdS{sub 5} shock wave. We find two physically meaningful extremal string configurations. For both solutions we obtain the forward scattering amplitude N for the quark dipole-nucleus scattering. We study the onset of unitarity with increasing center-of-mass energy and transverse size of the dipole: we observe that for both solutions the saturation scale Q{sub s} is independent of energy/Bjorken-x and depends on the atomic number of the nucleus as Q{sub s}{approx}A{sup 1/3}. Finally we observe that while one of the solutions we found corresponds to the pomeron intercept of {alpha}{sub P} = 2 found earlier in the literature, when extended to higher energy or larger dipole sizes it violates the black disk limit. The other solution we found respects the black disk limit and yields the pomeron intercept of {alpha}{sub P} = 1.5. We thus conjecture that the right pomeron intercept in gauge theories at strong coupling may be {alpha}{sub P} = 1.5.

  4. The Sun Health Research Institute Brain Donation Program: Description and Eexperience, 1987–2007

    PubMed Central

    Sue, Lucia I.; Walker, Douglas G.; Roher, Alex E.; Lue, LihFen; Vedders, Linda; Connor, Donald J.; Sabbagh, Marwan N.; Rogers, Joseph

    2008-01-01

    The Brain Donation Program at Sun Health Research Institute has been in continual operation since 1987, with over 1000 brains banked. The population studied primarily resides in the retirement communities of northwest metropolitan Phoenix, Arizona. The Institute is affiliated with Sun Health, a nonprofit community-owned and operated health care provider. Subjects are enrolled prospectively to allow standardized clinical assessments during life. Funding comes primarily from competitive grants. The Program has made short postmortem brain retrieval a priority, with a 2.75-h median postmortem interval for the entire collection. This maximizes the utility of the resource for molecular studies; frozen tissue from approximately 82% of all cases is suitable for RNA studies. Studies performed in-house have shown that, even with very short postmortem intervals, increasing delays in brain retrieval adversely affect RNA integrity and that cerebrospinal fluid pH increases with postmortem interval but does not predict tissue viability. PMID:18347928

  5. Bubbling AdS3

    NASA Astrophysics Data System (ADS)

    Martelli, Dario; Morales, Jose F.

    2005-02-01

    In the light of the recent Lin, Lunin, Maldacena (LLM) results, we investigate 1/2-BPS geometries in minimal (and next to minimal) supergravity in D = 6 dimensions. In the case of minimal supergravity, solutions are given by fibrations of a two-torus T2 specified by two harmonic functions. For a rectangular torus the two functions are related by a non-linear equation with rare solutions: AdS3 × S3, the pp-wave and the multi-center string. ``Bubbling'', i.e. superpositions of droplets, is accommodated by allowing the complex structure of the T2 to vary over the base. The analysis is repeated in the presence of a tensor multiplet and similar conclusions are reached, with generic solutions describing D1D5 (or their dual fundamental string-momentum) systems. In this framework, the profile of the dual fundamental string-momentum system is identified with the boundaries of the droplets in a two-dimensional plane.

  6. Evaluation of DNA degradation using flow cytometry: promising tool for postmortem interval determination.

    PubMed

    Williams, Teddric; Soni, Shivani; White, Jason; Can, Gunay; Javan, Gulnaz T

    2015-06-01

    Over the years, there have been numerous formulas proposed for use in determining the postmortem interval (PMI); however, no method is all encompassing and absolute. Even so, very little research has been undertaken to determine if there is a viable correlation between the rate of DNA degradation and PMI, which can be calculated from analysis by flow cytometry. In this study, we analyzed the rate of DNA degradation of spleen and brain tissues from 15 cadavers over a 96-hour period of time at 2 temperature conditions, that is, 21°C (room temperature) and 4°C (refrigerator) to mimic summer and winter weather, respectively. The resulting data were used to form a pattern that correlates DNA degradation to cell death occurrence. Statistical analyses were performed to determine the significance of the relationship between PMI and DNA degradation. Moreover, in search of alternative reliable organs of interest for PMI estimation, the results demonstrate that the brain has lesser DNA degradation as compared with the spleen. Thus, the current study suggests that the brain can be an organ of choice for PMI studies, but more research is underway in this aspect. PMID:25893913

  7. Brain investigation and brain conceptualization

    PubMed Central

    Redolfi, Alberto; Bosco, Paolo; Manset, David; Frisoni, Giovanni B.

    Summary The brain of a patient with Alzheimer’s disease (AD) undergoes changes starting many years before the development of the first clinical symptoms. The recent availability of large prospective datasets makes it possible to create sophisticated brain models of healthy subjects and patients with AD, showing pathophysiological changes occurring over time. However, these models are still inadequate; representations are mainly single-scale and they do not account for the complexity and interdependence of brain changes. Brain changes in AD patients occur at different levels and for different reasons: at the molecular level, changes are due to amyloid deposition; at cellular level, to loss of neuron synapses, and at tissue level, to connectivity disruption. All cause extensive atrophy of the whole brain organ. Initiatives aiming to model the whole human brain have been launched in Europe and the US with the goal of reducing the burden of brain diseases. In this work, we describe a new approach to earlier diagnosis based on a multimodal and multiscale brain concept, built upon existing and well-characterized single modalities. PMID:24139654

  8. Why We Need Postmortem Analysis of Cardiac Implantable Electronic Devices.

    PubMed

    Mauf, Sabrina; Jentzsch, Thorsten; Laberke, Patrick J; Thali, Michael J; Bartsch, Christine

    2016-07-01

    The prevalence of cardiac implantable electronic devices (CIEDs), pacemakers and implantable cardioverter defibrillators (ICDs) is increasing. However, postmortem analysis of CIEDs is not performed routinely. Fourteen consecutive CIEDs were analyzed. The indication for and date of implantation, technical data, CIED reprogramming, heart rhythm disturbances, patient demographics and medical consultations were investigated. Death during the first year after implantation was seen in 54%, whereof 71% consulted a physician within 10 days before death. The time of death was attributed to a particular day in 29%. There was a relationship between CIEDs and cause/manner of death in 50%. Although limited by a small sample size, this study advocates the routine postmortem CIED analysis for forensic and clinical purposes in selected cases. Patients with CIEDs seem to show an increased risk of death during the first year after implantation. The analysis of CIEDs can be helpful in evaluating the time/cause/manner of death. PMID:27364278

  9. Imaging maculopathy in post-mortem human eyes.

    PubMed

    Curcio, Christine A

    2005-12-01

    Age-related maculopathy (ARM) remains a poorly understood degeneration. To discover new pathways using contemporary genomics, proteomics, and immunohistochemistry, validate emerging animal models, and validate new imaging modalities, human tissues obtained from donor eyes will be essential to ARM research for the foreseeable future. Because fundus appearance is the clinical diagnostic lingua franca, laboratory investigators adapted these standards to the distinctive appearance of post-mortem tissues in order to identify and stage ARM in donor eyes. Post-mortem tissues offer unique advantages and limitations relative to pre-mortem tissues for imaging studies. One fellow eye can be used for imaging and the other for correlative laboratory studies, if some degree of disease stage asymmetry between eyes is acceptable. Histological verification is a necessary, albeit challenging, step in validating a grading system. PMID:16171840

  10. BrainNet Europe's Code of Conduct for brain banking.

    PubMed

    Klioueva, Natasja M; Rademaker, Marleen C; Dexter, David T; Al-Sarraj, Safa; Seilhean, Danielle; Streichenberger, Nathalie; Schmitz, Peer; Bell, Jeanne E; Ironside, James W; Arzberger, Thomas; Huitinga, Inge

    2015-07-01

    Research utilizing human tissue and its removal at post-mortem has given rise to many controversies in the media and posed many dilemmas in the fields of law and ethics. The law often lacks clear instructions and unambiguous guidelines. The absence of a harmonized international legislation with regard to post-mortem medical procedures and donation of tissue and organs contributes to the complexity of the issue. Therefore, within the BrainNet Europe (BNE) consortium, a consortium of 19 European brain banks, we drafted an ethical Code of Conduct for brain banking that covers basic legal rules and bioethical principles involved in brain banking. Sources include laws, regulations and guidelines (Declarations, Conventions, Recommendations, Guidelines and Directives) issued by international key organizations, such as the Council of Europe, European Commission, World Medical Association and World Health Organization. The Code of Conduct addresses fundamental topics as the rights of the persons donating their tissue, the obligations of the brain bank with regard to respect and observance of such rights, informed consent, confidentiality, protection of personal data, collections of human biological material and their management, and transparency and accountability within the organization of a brain bank. The Code of Conduct for brain banking is being adopted by the BNE network prior to being enshrined in official legislation for brain banking in Europe and beyond. PMID:25578485

  11. Haemorrhoids leading to post-mortem bleeding artefact.

    PubMed

    Kanchan, Tanuj; Menezes, Ritesh G; Manipady, Shahnavaz

    2006-07-01

    We present a case where a 54-year-old man suffering from haemorrhoids, committed suicide by hanging. Gravitational forces due to the upright position of the body facilitated post-mortem per-rectal bleeding from the ulcerated haemorrhoids. The bleeding stained his under garment and wrap around cloth. Frank blood was also seen on the floor beneath the hanging body. The blood at the crime scene was wrongly interpreted by the investigating police as that due to self-inflicted injury or possibly case of homicide followed by post-mortem suspension of the body. Observation of the crime scene by forensic medicine experts and subsequent autopsy findings revealed that the bleeding was from the haemorrhoids. This case is reported for its rarity, for the awareness of the possible post-mortem haemorrhoidal bleeding artefact, to explain the circumstances of such a possibility, and to emphasize the importance of involving forensic medicine experts as a part of the crime scene investigation team. PMID:16442833

  12. The Role of Postmortem Studies in Pneumonia Etiology Research

    PubMed Central

    Bunthi, Charatdao; Wonodi, Chizoba B.; Morpeth, Susan C.; Molyneux, Catherine S.; Zaki, Sherif R.; Levine, Orin S.; Murdoch, David R.; Scott, J. Anthony G.

    2012-01-01

    The diagnosis of etiology in severe pneumonia remains a challenging area. Postmortem lung tissue potentially increases the sensitivity of investigations for identification of causative pathogens in fatal cases of pneumonia and can confirm antemortem microbiological diagnoses. Tissue sampling allows assessment of histological patterns of disease and ancillary immunohistochemical or molecular diagnostic techniques. It may also enhance the recognition of noninfectious conditions that clinically simulate acute pneumonia. Biobanking of lung tissue or postmortem culture isolates offers opportunities for new pathogen discovery and research into host-pathogen interactions. The Pneumonia Etiology Research for Child Health study proposes a percutaneous needle biopsy approach to obtain postmortem samples, rather than a full open autopsy. This has the advantage of greater acceptability to relatives, but risks greater sampling error. Both approaches may be susceptible to microbiological contamination or pathogen degradation. However, previous autopsy studies have confirmed the value of histological examination in revealing unsuspected pathogens and influencing clinical guidelines for the diagnosis and treatment of future pneumonia cases. PMID:22403232

  13. Interpretation of postmortem forensic toxicology results for injury prevention research.

    PubMed

    Drummer, Olaf H; Kennedy, Briohny; Bugeja, Lyndal; Ibrahim, Joseph Elias; Ozanne-Smith, Joan

    2013-08-01

    Forensic toxicological data provides valuable insight into the potential contribution of alcohol and drugs to external-cause deaths. There is a paucity of material that guides injury researchers on the principles that need to be considered when examining the presence and contribution of alcohol and drugs to these deaths. This paper aims to describe and discuss strengths and limitations of postmortem forensic toxicology sample selection, variations in analytical capabilities and data interpretation for injury prevention research. Issues to be considered by injury researchers include: the circumstances surrounding death (including the medical and drug use history of the deceased person); time and relevant historical factors; postmortem changes (including redistribution and instability); laboratory practices; specimens used; drug concentration; and attribution of contribution to death. This paper describes the range of considerations for testing and interpreting postmortem forensic toxicology, particularly when determining impairment or toxicity as possible causal factors in injury deaths. By describing these considerations, this paper has application to decisions about study design and case inclusion in injury prevention research, and to the interpretation of research findings. PMID:23197673

  14. Estimating Time Since Death from Postmortem Human Gut Microbial Communities.

    PubMed

    Hauther, Kathleen A; Cobaugh, Kelly L; Jantz, Lee Meadows; Sparer, Tim E; DeBruyn, Jennifer M

    2015-09-01

    Postmortem succession of human-associated microbial communities ("human microbiome") has been suggested as a possible method for estimating postmortem interval (PMI) for forensic analyses. Here we evaluate human gut bacterial populations to determine quantifiable, time-dependent changes postmortem. Gut microflora were repeatedly sampled from the proximal large intestine of 12 deceased human individuals as they decayed under environmental conditions. Three intestinal bacterial genera were quantified by quantitative PCR (qPCR) using group-specific primers targeting 16S rRNA genes. Bacteroides and Lactobacillus relative abundances declined exponentially with increasing PMI at rates of Nt=0.977e(-0.0144t) (r2=0.537, p<0.001) and Nt=0.019e(-0.0087t) (r2=0.396, p<0.001), respectively, where Nt is relative abundance at time (t) in cumulative degree hours. Bifidobacterium relative abundances did not change significantly: Nt=0.003e(-0.002t) (r2=0.033, p=0.284). Therefore, Bacteroides and Lactobacillus abundances could be used as quantitative indicators of PMI. PMID:26096156

  15. Postmortem computed tomography in victims of military air mishaps: radiological-pathological correlation of CT findings.

    PubMed

    Levy, Gad; Goldstein, Liav; Blachar, Arye; Apter, Sara; Barenboim, Erez; Bar-Dayan, Yaron; Shamis, Ari; Atar, Eli

    2007-10-01

    A thorough medical inquiry is included in every aviation mishap investigation. While the gold standard of this investigation is a forensic pathology examination, numerous reports stress the important role of computed tomography in the postmortem evaluation of trauma victims. To characterize the findings identified by postmortem CT and compare its performance to conventional autopsy in victims of military aviation mishaps, we analyzed seven postmortem CT examinations. Musculoskeletal injuries accounted for 57.8% of the traumatic findings identified by postmortem CT. The most frequent findings were fractures of the rib (47%), skull (9.6%) and facial bones (8.6%). Abnormally located air accounted for 24% of findings, for which CT was superior (3.5% detected by autopsy, 100% by postmortem CT, P < 0.001). The performance of autopsy in detecting injuries was superior (autopsy detected 85.8% of all injuries, postmortem CT detected 53.9%, P < 0.001), especially in the detection of superficial lesions (100% detected by autopsy, 10.5% by postmortem CT, P < 0.001) and solid organ injuries (100% by autopsy, 18.5% by postmortem CT, P < 0.001). Performance in the detection of musculoskeletal injuries was similar (91.3% for autopsy, 90.3% for postmortem CT, P = not significant). Postmortem CT and autopsy have distinct performance profiles, and although the first cannot replace the latter it is a useful complementary examination. PMID:17987755

  16. Postmortem MRI: a novel window into the neurobiology of late life cognitive decline.

    PubMed

    Dawe, Robert J; Yu, Lei; Leurgans, Sue E; Schneider, Julie A; Buchman, Aron S; Arfanakis, Konstantinos; Bennett, David A; Boyle, Patricia A

    2016-09-01

    This study tested the hypothesis that indices of brain tissue integrity derived from postmortem magnetic resonance imaging (MRI) are associated with late life decline in cognitive function and dementia, over and above contributions from common age-related neuropathologies. Cerebral hemispheres were obtained from 425 deceased older adults who had undergone 2 or more annual cognitive assessments, which included clinical diagnosis of dementia. Specimens underwent MRI to produce maps of transverse relaxation rate, R2. Voxelwise regression revealed brain regions where R2 was associated with cognitive decline. We then used random effects models to quantify the extent to which R2 accounted for variation in decline, after adjustment for demographics and neuropathologic indices of the 3 most common causes of dementia: Alzheimer's disease, cerebrovascular disease, and Lewy body disease. We additionally tested whether R2 was tied to greater likelihood of clinical diagnosis of Alzheimer's dementia using logistic regression models. During an average of 8.1 years, the mean rate of decline in global cognitive function was 0.13 unit per year (p < 0.0001). The tissue alteration most commonly related to decline was R2 slowing in white matter. Each unit decrease in R2 was associated with an additional 0.053-unit per year steepening of the rate of global cognitive decline (p < 0.001). Furthermore, R2 accounted for 8.4% of the variance in rate of global cognitive decline, above and beyond the 26.5% accounted for by demographics and neuropathologic indices, and 7.1%-11.2% of the variance of the decline rates in episodic, semantic, and working memory and perceptual speed. Alterations in R2 were also related to an increased odds of clinical diagnosis of Alzheimer's dementia (odds ratio = 2.000, 95% confidence interval 1.600, 2.604). Therefore, postmortem MRI indices of brain tissue integrity, particularly in white matter, are useful for elucidating the basis of late life cognitive

  17. Involvement of neuroleptic drugs in selenium deficiency and sudden death of cardiac origin: study and human post-mortem examination.

    PubMed

    Hamdan, Lamia; Bost, Muriel; Chazot, Guy; Bui-Xuan, Bernard; Vaillant, Fanny; Dehina, Leila; Descotes, Jacques; Tabib, Alain; Mamou, Zahida; Timour, Quadiri

    2012-06-01

    The involvement of psychotropic drugs in sudden deaths has been highlighted. The objective of this work was to establish a link between selenium levels in heart tissue, psychotropic treatment and sudden death. Selenium levels were measured by electrothermal atomic absorption spectroscopy post-mortem in heart, brain and liver. Histological examination evidenced dilated cardiomyopathy in 45% of cases, left ventricular hypertrophy in 36%, and ischemic coronaropathy in 18%. A significant reduction of myocardial selenium levels compared to controls was seen in patients treated with neuroleptic drugs or meprobamate. No changes in brain or liver selenium levels were seen. These results suggest that selenium deficiency can facilitate sudden death in patients on psychotropic drugs. The reduced activity of glutathione peroxidase due to selenium deficiency can result in augmented oxidative stress in myocardial cells and myocardiopathy leading to sudden death. PMID:22664334

  18. Brain region-specific monoaminergic correlates of neuropsychiatric symptoms in Alzheimer's disease.

    PubMed

    Vermeiren, Yannick; Van Dam, Debby; Aerts, Tony; Engelborghs, Sebastiaan; De Deyn, Peter P

    2014-01-01

    Neuropsychiatric symptoms (NPS) in Alzheimer's disease (AD) are present during the disease course of nearly all AD patients and consist of psychosis, agitation/aggression, and depression, among others. Given their detrimental consequences regarding life expectancy, cognition, and socio-economic costs, it is essential to elucidate their neurochemical etiology to facilitate the development of novel and effective pharmacotherapeutics. This study attempted to identify brain region-specific monoaminergic correlates of NPS by measuring the levels of eight monoamines and metabolites in nine relevant postmortem brain regions of 40 behaviorally characterized AD patients, i.e., dopamine (DA), serotonin (5-HT), (nor)epinephrine and their respective metabolites 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid, 5-hydroxy-3-indoleacetic acid (5-HIAA), and 3-methoxy-4-hydroxyphenylglycol (MHPG), using RP-HPLC-ECD. Likewise, Mini-Mental State Examination (MMSE) score correlates of monoaminergic neurotransmitter alterations were calculated. As a result, MMSE scores, used as a measure of dementia severity, correlated positively with hippocampal 5-HIAA levels as well as with 5-HT levels of the superior temporal gyrus and cerebellar cortex. Furthermore, hippocampal 5-HIAA levels inversely correlated with agitation scores, whereas thalamic MHPG levels comparably did with the presence of hallucinations. Finally, in the cerebellar cortex, DOPAC/DA ratios, indicative of DA turnover, correlated with physically agitated behavior while MHPG levels correlated with affective disturbances. These findings support the assumption that specific NPS features in AD might be (in)directly related to brain region-specific monoaminergic neurotransmitter alterations. Additionally, the effect of AD pathology on neurochemical alterations in the cerebellum requires further examination due to its important but underestimated role in the neurochemical pathophysiology of NPS in AD. PMID:24685637

  19. Using single nuclei for RNA-seq to capture the transcriptome of postmortem neurons

    PubMed Central

    Krishnaswami, Suguna Rani; Grindberg, Rashel V; Novotny, Mark; Venepally, Pratap; Lacar, Benjamin; Bhutani, Kunal; Linker, Sara B; Pham, Son; Erwin, Jennifer A; Miller, Jeremy A; Hodge, Rebecca; McCarthy, James K; Kelder, Martin; McCorrison, Jamison; Aevermann, Brian D; Fuertes, Francisco Diez; Scheuermann, Richard H; Lee, Jun; Lein, Ed S; Schork, Nicholas; McConnell, Michael J; Gage, Fred H; Lasken, Roger S

    2016-01-01

    A protocol is described for sequencing the transcriptome of a cell nucleus. Nuclei are isolated from specimens and sorted by FACS, cDNA libraries are constructed and RNA-seq is performed, followed by data analysis. Some steps follow published methods (Smart-seq2 for cDNA synthesis and Nextera XT barcoded library preparation) and are not described in detail here. Previous single-cell approaches for RNA-seq from tissues include cell dissociation using protease treatment at 30 °C, which is known to alter the transcriptome. We isolate nuclei at 4 °C from tissue homogenates, which cause minimal damage. Nuclear transcriptomes can be obtained from postmortem human brain tissue stored at −80 °C, making brain archives accessible for RNA-seq from individual neurons. The method also allows investigation of biological features unique to nuclei, such as enrichment of certain transcripts and precursors of some noncoding RNAs. By following this procedure, it takes about 4 d to construct cDNA libraries that are ready for sequencing. PMID:26890679

  20. Using single nuclei for RNA-seq to capture the transcriptome of postmortem neurons.

    PubMed

    Krishnaswami, Suguna Rani; Grindberg, Rashel V; Novotny, Mark; Venepally, Pratap; Lacar, Benjamin; Bhutani, Kunal; Linker, Sara B; Pham, Son; Erwin, Jennifer A; Miller, Jeremy A; Hodge, Rebecca; McCarthy, James K; Kelder, Martin; McCorrison, Jamison; Aevermann, Brian D; Fuertes, Francisco Diez; Scheuermann, Richard H; Lee, Jun; Lein, Ed S; Schork, Nicholas; McConnell, Michael J; Gage, Fred H; Lasken, Roger S

    2016-03-01

    A protocol is described for sequencing the transcriptome of a cell nucleus. Nuclei are isolated from specimens and sorted by FACS, cDNA libraries are constructed and RNA-seq is performed, followed by data analysis. Some steps follow published methods (Smart-seq2 for cDNA synthesis and Nextera XT barcoded library preparation) and are not described in detail here. Previous single-cell approaches for RNA-seq from tissues include cell dissociation using protease treatment at 30 °C, which is known to alter the transcriptome. We isolate nuclei at 4 °C from tissue homogenates, which cause minimal damage. Nuclear transcriptomes can be obtained from postmortem human brain tissue stored at -80 °C, making brain archives accessible for RNA-seq from individual neurons. The method also allows investigation of biological features unique to nuclei, such as enrichment of certain transcripts and precursors of some noncoding RNAs. By following this procedure, it takes about 4 d to construct cDNA libraries that are ready for sequencing. PMID:26890679

  1. Morphine-3-D glucuronide stability in postmortem specimens exposed to bacterial enzymatic hydrolysis.

    PubMed

    Carroll, F T; Marraccini, J V; Lewis, S; Wright, W

    2000-12-01

    Medical examiners frequently rely on the finding of free morphine present in postmortem specimens to assist in certifying deaths associated with narcotics. In vitro hydrolysis of morphine-3-D glucuronide (M3DG) to free morphine was studied using variable specimen pH, initial degree of specimen putrefaction, storage temperature and time, and the effectiveness of sodium fluoride (NaF) preservation. Reagent M3DG was added to opiate-free fresh blood and urine and to autopsy-derived blood specimens. Reagent bovine glucuronidase was also added to certain specimens. Freshly collected and refrigerated NaF-preserved blood produced minimal free morphine, whereas four of five autopsy blood specimens produced free morphine from M3DG. Increased storage time, temperature, and initial degree of putrefaction resulted in greater free morphine generation despite the absence of viable bacteria. Hydrolysis occurring during specimen storage can generate free morphine from M3DG and may result in erroneous conclusions in certifying narcotic deaths. PMID:11111790

  2. Consequences of Aberrant Insulin Regulation in the Brain: Can Treating Diabetes be Effective for Alzheimer’s Disease

    PubMed Central

    Arab, L; Sadeghi, R; Walker, D.G; Lue, L-F; Sabbagh, M.N

    2011-01-01

    There is an urgent need for new ways to treat Alzheimer’s disease (AD), the most common cause of dementia in the elderly. Current therapies are modestly effective at treating the symptoms, and do not significantly alter the course of the disease. Over the years, a range of epidemiological and experimental studies have demonstrated interactions between diabetes mellitus and AD. As both diseases are leading causes of morbidity and mortality in the elderly and are frequent co-morbid conditions, it has raised the possibility that treating diabetes might be effective in slowing AD. This is currently being attempted with drugs such as the insulin sensitizer rosiglitazone. These two diseases share many clinical and biochemical features, such as elevated oxidative stress, vascular dysfunction, amyloidogenesis and impaired glucose metabolism suggesting common pathogenic mechanisms. The main thrust of this review will be to explore the evidence from a pathological point of view to determine whether diabetes can cause or exacerbate AD. This was supported by a number of animal models of AD that have been shown to have enhanced pathology when diabetic conditions were induced. The one drawback in linking diabetes and insulin to AD has been the postmortem studies of diabetic brains demonstrating that AD pathology was not increased; in fact decreased pathology has often been reported. In addition, diabetes induces its own distinct features of neuropathology different from AD. There are common pathological features to be considered including vascular abnormalities, a major feature arising from diabetes; there is increasing evidence that vascular abnormalities can contribute to AD. The most important common mechanism between insulin-resistant (type II) diabetes and AD could be impaired insulin signaling; a form of toxic amyloid can damage neuronal insulin receptors and affect insulin signaling and cell survival. It has even been suggested that AD could be considered as “type 3

  3. Smartphone Image Acquisition During Postmortem Monocular Indirect Ophthalmoscopy.

    PubMed

    Lantz, Patrick E; Schoppe, Candace H; Thibault, Kirk L; Porter, William T

    2016-01-01

    The medical usefulness of smartphones continues to evolve as third-party applications exploit and expand on the smartphones' interface and capabilities. This technical report describes smartphone still-image capture techniques and video-sequence recording capabilities during postmortem monocular indirect ophthalmoscopy. Using these devices and techniques, practitioners can create photographic documentation of fundal findings, clinically and at autopsy, without the expense of a retinal camera. Smartphone image acquisition of fundal abnormalities can promote ophthalmological telemedicine--especially in regions or countries with limited resources--and facilitate prompt, accurate, and unbiased documentation of retinal hemorrhages in infants and young children. PMID:26248715

  4. Searching human brain for mechanisms of psychiatric disorders. Implications for studies on schizophrenia.

    PubMed

    Berretta, Sabina; Heckers, Stephan; Benes, Francine M

    2015-09-01

    In the past 25years, research on the human brain has been providing a clear path toward understanding the pathophysiology of psychiatric illnesses. The successes that have been accrued are matched by significant difficulties identifying and controlling a large number of potential confounding variables. By systematically and effectively accounting for unwanted variance in data from imaging and postmortem human brain studies, meaningful and reliable information regarding the pathophysiology of human brain disorders can be obtained. This perspective paper focuses on postmortem investigations to discuss some of the most challenging sources of variance, including diagnosis, comorbidity, substance abuse and pharmacological treatment, which confound investigations of the human brain. PMID:25458567

  5. Chronic Pyruvate Supplementation Increases Exploratory Activity and Brain Energy Reserves in Young and Middle-Aged Mice

    PubMed Central

    Koivisto, Hennariikka; Leinonen, Henri; Puurula, Mari; Hafez, Hani Sayed; Barrera, Glenda Alquicer; Stridh, Malin H.; Waagepetersen, Helle S.; Tiainen, Mika; Soininen, Pasi; Zilberter, Yuri; Tanila, Heikki

    2016-01-01

    Numerous studies have reported neuroprotective effects of pyruvate when given in systemic injections. Impaired glucose uptake and metabolism are found in Alzheimer’s disease (AD) and in AD mouse models. We tested whether dietary pyruvate supplementation is able to provide added energy supply to brain and thereby attenuate aging- or AD-related cognitive impairment. Mice received ~800 mg/kg/day Na-pyruvate in their chow for 2–6 months. In middle-aged wild-type mice and in 6.5-month-old APP/PS1 mice, pyruvate facilitated spatial learning and increased exploration of a novel odor. However, in passive avoidance task for fear memory, the treatment group was clearly impaired. Independent of age, long-term pyruvate increased explorative behavior, which likely explains the paradoxical impairment in passive avoidance. We also assessed pyruvate effects on body weight, muscle force, and endurance, and found no effects. Metabolic postmortem assays revealed increased energy compounds in nuclear magnetic resonance spectroscopy as well as increased brain glycogen storages in the pyruvate group. Pyruvate supplementation may counteract aging-related behavioral impairment, but its beneficial effect seems related to increased explorative activity rather than direct memory enhancement. PMID:27014054

  6. Estimation of Pork Quality Traits Using Exsanguination Blood and Postmortem Muscle Metabolites

    PubMed Central

    Choe, J. H.; Choi, M. H.; Ryu, Y. C.; Go, G. W.; Choi, Y. M.; Lee, S. H.; Lim, K. S.; Lee, E. A.; Kang, J. H.; Hong, K. C.; Kim, B. C.

    2015-01-01

    The current study was designed to estimate the pork quality traits using metabolites from exsanguination blood and postmortem muscle simultaneously under the Korean standard pre- and post-slaughter conditions. A total of 111 Yorkshire (pure breed and castrated male) pigs were evaluated under the Korean standard conditions. Measurements were taken of the levels of blood glucose and lactate at exsanguination, and muscle glycogen and lactate content at 45 min and 24 h postmortem. Certain pork quality traits were also evaluated. Correlation analysis and multiple regression analysis including stepwise regression were performed. Exsanguination blood glucose and lactate levels were positively correlated with each other, negatively related to postmortem muscle glycogen content and positively associated with postmortem muscle lactate content. A rapid and extended postmortem glycolysis was associated with high levels of blood glucose and lactate, with high muscle lactate content, and with low muscle glycogen content during postmortem. In addition, these were also correlated with paler meat color and reduced water holding capacity. The results of multiple regression analyses also showed that metabolites in exsanguination blood and postmortem muscle explained variations in pork quality traits. Especially, levels of blood glucose and lactate and content of muscle glycogen at early postmortem were significantly associated with an elevated early glycolytic rate. Furthermore, muscle lactate content at 24 h postmortem alone accounted for a considerable portion of the variation in pork quality traits. Based on these results, the current study confirmed that the main factor influencing pork quality traits is the ultimate lactate content in muscle via postmortem glycolysis, and that levels of blood glucose and lactate at exsanguination and contents of muscle glycogen and lactate at postmortem can explain a large portion of the variation in pork quality even under the standard

  7. Postmortem examinations on deceased neonates: a rarely utilized procedure in an African referral center.

    PubMed

    Ugiagbe, Ezekiel E; Osifo, Osarumwense D

    2012-01-01

    Postmortem examination remains the gold standard for the correct diagnosis of many diseases and for unraveling unexplained causes of death. This paper reports on the poor utilization of autopsy services and encourages parents/caregivers and practitioners to perform postmortem examinations on deceased neonates in sub-Saharan Africa. In a retrospective study, the records of 1093 neonates (653 males and 440 females, ratio 1.5∶1) who died at the University of Benin Teaching Hospital and who were brought to the mortuary between 2006 and 2010 were reviewed to determine the utilization of and factors influencing postmortem examination. Sixty-two percent of the neonates died within the 1st week of life, and only 9 (0.8%) underwent a postmortem examination. Findings in the 9 postmortem studies performed on 7 males and 2 females provided additional information on the causes of death. The religious beliefs that neonates should not be subjected to postmortem study and beliefs that dead neonates are taboo and a punishment by the gods for past wrongdoings influenced 511 (46.8%) parents/caregivers to refuse postmortem analysis. The practitioners did not request postmortem study in 281 (25.7%) of the cases. The utilization of postmortem examination was marginal in this setting. We advocate the need for public enlightenment campaigns to modify the attitudes of parents/caregivers toward the postmortem study of deceased neonates. Policies should be formulated to mandate postmortem examinations of deceased neonates to enhance insight into neonatal disease, unravel unexplained causes of death, and improve the standard of neonatal care in this subregion. PMID:21991941

  8. Carbon monoxide stability in stored postmortem blood samples.

    PubMed

    Kunsman, G W; Presses, C L; Rodriguez, P

    2000-10-01

    Carbon monoxide (CO) poisoning remains a common cause of both suicidal and accidental deaths in the United States. As a consequence, determination of the percent carboxyhemoglobin (%COHb) level in postmortem blood is a common analysis performed in toxicology laboratories. The blood specimens analyzed are generally preserved with either EDTA or sodium fluoride. Potentially problematic scenarios that may arise in conjunction with CO analysis are a first analysis or a reanalysis requested months or years after the initial toxicology testing is completed; both raise the issue of the stability of carboxyhemoglobin in stored postmortem blood specimens. A study was conducted at the Bexar County Medical Examiner's Office to evaluate the stability of CO in blood samples collected in red-, gray-, and purple-top tubes by comparing results obtained at the time of the autopsy and after two years of storage at 3 degrees C using either an IL 282 or 682 CO-Oximeter. The results from this study suggest that carboxyhemoglobin is stable in blood specimens collected in vacutainer tubes, with or without preservative, and stored refrigerated for up to two years. PMID:11043662

  9. Mitragynine 'Kratom' related fatality: a case report with postmortem concentrations.

    PubMed

    McIntyre, Iain M; Trochta, Amber; Stolberg, Susan; Campman, Steven C

    2015-03-01

    A 24-year-old man whose medical history was significant for alcohol abuse and depression was found unresponsive in bed. He had several prior suicide attempts with 'pills' and had also been hospitalized for an accidental overdose on a previous occasion. Autopsy findings were unremarkable apart from pulmonary edema and congestion, and urinary retention. Postmortem peripheral blood initially screened positive for mitragynine 'Kratom' (by routine alkaline drug screen by gas chromatography-mass spectrometry, GC-MS), which was subsequently confirmed by a specific GC-MS selective ion mode analysis following solid-phase extraction. Concentrations were determined in the peripheral blood (0.23 mg/L), central blood (0.19 mg/L), liver (0.43 mg/kg), vitreous (<0.05 mg/L), urine (0.37 mg/L) and was not detected in the gastric. Therapeutic concentrations of venlafaxine, diphenhydramine and mirtazapine were also detected together with a negligible ethanol of 0.02% (w/v). The results are discussed in relation to previous cases of toxicity, and the lack of potential for mitragynine postmortem redistribution. PMID:25516573

  10. Building models for postmortem abnormalities in hippocampus of schizophrenics.

    PubMed

    Benes, Francine M

    2015-09-01

    Postmortem studies have suggested that there is abnormal GABAergic activity in the hippocampus in schizophrenia (SZ). In micro-dissected human hippocampal slices, a loss of interneurons and a compensatory upregulation of GABAA receptor binding activity on interneurons, but not PNs, has suggested that disinhibitory GABA-to-GABA connections are abnormal in stratum oriens (SO) of CA3/2, but not CA1, in schizophrenia. Abnormal expression changes in the expression of kainate receptor (KAR) subunits 5, 6 and 7, as well as an inwardly-rectifying hyperpolarization-activated cationic channel (Ih3; HCN3) may play important roles in regulating GABA cell activity at the SO CA3/2 locus. The exclusive neurons at this site are GABAergic interneurons; these cells also receive direct projections from the basolateral amygdala (BLA). When the BLA is stimulated by stereotaxic infusion of picrotoxin in rats, KARs influence axodendritic and presynaptic inhibitory mechanisms that regulate both inhibitory and disinhibitory interneurons in the SO-CA3/2 locus. The rat model described here was specifically developed to extend our understanding of these and other postmortem findings and has suggested that GABAergic abnormalities and possible disturbances in oscillatory rhythms may be related to a dysfunction of disinhibitory interneurons at the SO-CA3/2 site of schizophrenics. PMID:25749020

  11. Postmortem biochemistry in suspected starvation-induced ketoacidosis.

    PubMed

    Palmiere, Cristian; Tettamanti, Camilla; Augsburger, Marc; Burkhardt, Sandra; Sabatasso, Sara; Lardi, Christelle; Werner, Dominique

    2016-08-01

    Significantly increased blood ketone body levels can be occasionally observed in the forensic setting in situations other than exposure to cold, diabetic or alcoholic ketoacidosis. Though infrequent, these cases do occur and deserve thorough evaluation in order to establish appropriate differential diagnoses and quantify the role that hyperketonemia may play in the death process. Starvation ketoacidosis is a rare cause of metabolic acidosis and is a phenomenon that occurs normally during fasting, as the body switches from carbohydrate to lipid energy sources. The levels of ketonemia in starvation ketoacidosis is usually mild in comparison to those seen in diabetic or alcoholic ketoacidosis. In the clinical setting, several cases of starvation-induced ketoacidosis mainly associated with gastric banding, pregnancy, malnutrition and low-carbohydrate diets have been reported. However, starvation ketosis causing severe metabolic acidosis has been rarely described in the medical literature. In the realm of forensic pathology, starvation-induced hyperketonemia has been rarely described. In this paper we present the postmortem biochemical results observed in situations of suspected starvation-induced hyperketonemia that underwent medico-legal examination. In all these cases, the diagnosis of starvation induced-hyperketonemia and the subsequent ketoacidosis was established per exclusionem based on all postmortem investigation findings. A review of the literature pertaining to the clinical diagnosis of starvation ketoacidosis is also provided. PMID:27239954

  12. Postmortem diagnosis of drug-induced anaphylactic death.

    PubMed

    Palmiere, Cristian

    2016-07-01

    Kounis syndrome is defined as the concurrence of acute coronary syndromes including coronary spasm, acute myocardial infarction, and stent thrombosis, together with conditions associated with mast cell and platelet activation, involving interrelated and interacting inflammatory cells. Mast cells influence the inflammatory process decisively, though they are numerically inferior in this inflammatory cascade. Accumulation of eosinophils and mast cells in the splenic red pulp is frequently observed in anaphylactic deaths and can be considered a reliable finding for the postmortem diagnosis of this condition. Moreover, a high concentration of mast cell tryptase in serum and increased numbers of eosinophils and mast cells in the spleen make the diagnosis of anaphylactic death almost conclusive. Increased mast cell tryptase levels in postmortem serum, individually considered, do not allow the diagnosis of anaphylaxis-related death to be reached. On the other hand, neither does identification of mast cells and eosinophils within the coronary artery wall and the myocardium, individually considered, allow the hypothesis of anaphylaxis-related death to be formulated. PMID:27111724

  13. Interpretation of postmortem change in cadavers in Spain.

    PubMed

    Prieto, José L; Magaña, Concepción; Ubelaker, Douglas H

    2004-09-01

    Estimating time since death is especially difficult in the examination of poorly preserved cadavers and depends on the experience of the examiner and comparison with previously documented cases showing similar characteristics. The present study reports on information obtained over the past ten years through the work of the Laboratorio de Antropología y Odontología Forense (LAF) of the Instituto Anatómico Forense de Madrid, Spain, in particular evaluating how the type of fracture influences postmortem change. From the original 225 forensic cases examined between 1992 and 2002 in the LAF, a sample of 29 cases were selected from various regions of the Spanish mainland. A data collection protocol was established to reflect factors which the existing specialized literature, documenting the relation existing in the sample analyzed between time since death and the extent of postmortem change, which in the environments examined are distributed into the following phases: Phase 1 (putrefaction): one week to one month on the surface and two months in water. Phase 2 (initial skeletonization): two months on the surface and five to six months in water. Phase 3 (advanced skeltonization): six months to 1.5 years on the surface and 2.5 years buried. Phase 4 (complete skeletonization): about one year on the surface and three years buried. This paper also provide useful information on the impact of carrion insect activity, location, climate, seasonality, and predator. PMID:15461090

  14. Effect of postmortem aging time on tumbling marination performance of broiler breast fillets

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Previous data demonstrated that water-holding capacity (WHC), as measured by the salt-induced water uptake method, increases with aging up to 24 h postmortem in early-deboned chicken breast fillets (pectoralis major). Therefore, it was hypothesized that 24 h postmortem aging may enhance marination ...

  15. Effect of pH and postmortem aging on protein extraction from broiler breast muscle

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The objective of this study was to determine the effects of extraction buffer pH and postmortem aging on the extraction of salt-soluble and water-soluble proteins from broiler pectoralis muscle. De-boned broiler breast fillets were collected at 4 h postmortem, packaged, and then stored at 4°C until...

  16. Effects of postmortem aging and hydrodynamic pressure processing on sarcoplasmic proteins and beef tenderness

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The objective of this study was to determine the effects of hydrodynamic pressure processing (HDP) and postmortem aging on the sarcoplasmic protein fraction of beef strip loins. Loins (n=12) were halved at 48 h postmortem and assigned to HDP or control treatments. Following treatment, each half was ...

  17. 42 CFR 35.16 - Autopsies and other post-mortem operations.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... Section 35.16 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES MEDICAL CARE... located to permit an autopsy or such other post-mortem operation under the circumstances of the particular... the autopsy or other post-mortem operation shall be observed. Documents embodying consent shall...

  18. 42 CFR 35.16 - Autopsies and other post-mortem operations.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... Section 35.16 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES MEDICAL CARE... located to permit an autopsy or such other post-mortem operation under the circumstances of the particular... the autopsy or other post-mortem operation shall be observed. Documents embodying consent shall...

  19. 42 CFR 35.16 - Autopsies and other post-mortem operations.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... Section 35.16 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES MEDICAL CARE... located to permit an autopsy or such other post-mortem operation under the circumstances of the particular... the autopsy or other post-mortem operation shall be observed. Documents embodying consent shall...

  20. 42 CFR 35.16 - Autopsies and other post-mortem operations.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... Section 35.16 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES MEDICAL CARE... located to permit an autopsy or such other post-mortem operation under the circumstances of the particular... the autopsy or other post-mortem operation shall be observed. Documents embodying consent shall...

  1. 42 CFR 35.16 - Autopsies and other post-mortem operations.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 42 Public Health 1 2011-10-01 2011-10-01 false Autopsies and other post-mortem operations. 35.16 Section 35.16 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES MEDICAL CARE AND EXAMINATIONS HOSPITAL AND STATION MANAGEMENT General § 35.16 Autopsies and other post-mortem operations. Autopsies, or other...

  2. Effect of postmortem aging on marination performance of broiler breast pectoralis major categorized by color lightness

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The objective was to evaluate the effect of postmortem aging on marinade uptake and retention by early-deboned chicken breast fillets with different color lightness. Effects of marination on product yield and muscle shear force were also determined. Early deboned (2 h postmortem) broiler butterflies...

  3. Postmortem chemical changes in poultry breast meat monitored with visible-near infrared spectroscopy

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Chicken meat undergoes significant chemical and structural changes with postmortem time that influence meat quality characteristics. The objective of this study was to measure the visible-near infrared (vis-NIR) spectral differences in broiler breast fillets at 0.5, 4, 24, and 120 h postmortem. Mu...

  4. Polarised black holes in AdS

    NASA Astrophysics Data System (ADS)

    Costa, Miguel S.; Greenspan, Lauren; Oliveira, Miguel; Penedones, João; Santos, Jorge E.

    2016-06-01

    We consider solutions in Einstein-Maxwell theory with a negative cosmological constant that asymptote to global AdS 4 with conformal boundary {S}2× {{{R}}}t. At the sphere at infinity we turn on a space-dependent electrostatic potential, which does not destroy the asymptotic AdS behaviour. For simplicity we focus on the case of a dipolar electrostatic potential. We find two new geometries: (i) an AdS soliton that includes the full backreaction of the electric field on the AdS geometry; (ii) a polarised neutral black hole that is deformed by the electric field, accumulating opposite charges in each hemisphere. For both geometries we study boundary data such as the charge density and the stress tensor. For the black hole we also study the horizon charge density and area, and further verify a Smarr formula. Then we consider this system at finite temperature and compute the Gibbs free energy for both AdS soliton and black hole phases. The corresponding phase diagram generalizes the Hawking-Page phase transition. The AdS soliton dominates the low temperature phase and the black hole the high temperature phase, with a critical temperature that decreases as the external electric field increases. Finally, we consider the simple case of a free charged scalar field on {S}2× {{{R}}}t with conformal coupling. For a field in the SU(N ) adjoint representation we compare the phase diagram with the above gravitational system.

  5. T-cell brain infiltration and immature antigen-presenting cells in transgenic models of Alzheimer's disease-like cerebral amyloidosis.

    PubMed

    Ferretti, M T; Merlini, M; Späni, C; Gericke, C; Schweizer, N; Enzmann, G; Engelhardt, B; Kulic, L; Suter, T; Nitsch, R M

    2016-05-01

    Cerebral beta-amyloidosis, one of the pathological hallmarks of Alzheimer's disease (AD), elicits a well-characterised, microglia-mediated local innate immune response. In contrast, it is not clear whether cells of the adaptive immune system, in particular T-cells, react to cerebral amyloidosis in AD. Even though parenchymal T-cells have been described in post-mortem brains of AD patients, it is not known whether infiltrating T-cells are specifically recruited to the extracellular deposits of beta-amyloid, and whether they are locally activated into proliferating, effector cells upon interaction with antigen-presenting cells (APCs). To address these issues we have analysed by confocal microscopy and flow-cytometry the localisation and activation status of both T-cells and APCs in transgenic (tg) mice models of AD-like cerebral amyloidosis. Increased numbers of infiltrating T-cells were found in amyloid-burdened brain regions of tg mice, with concomitant up-regulation of endothelial adhesion molecules ICAM-1 and VCAM-1, compared to non-tg littermates. The infiltrating T-cells in tg brains did not co-localise with amyloid plaques, produced less interferon-gamma than those in controls and did not proliferate locally. Bona-fide dendritic cells were virtually absent from the brain parenchyma of both non-tg and tg mice, and APCs from tg brains showed an immature phenotype, with accumulation of MHC-II in intracellular compartments. These results indicate that cerebral amyloidosis promotes T-cell infiltration but interferes with local antigen presentation and T-cell activation. The inability of the brain immune surveillance to orchestrate a protective immune response to amyloid-beta peptide might contribute to the accumulation of amyloid in the progression of the disease. PMID:26872418

  6. A forensic toxicological dilemma: the interpretation of post-mortem concentrations of central acting analgesics.

    PubMed

    Daldrup, Th

    2004-06-10

    Dora V., a 88-year-old pensioner suffering from a hiatus hernia, died at the home of an orthopaedist and his wife, an anaesthetist, immediately after she had received a dose of 300 mg pethidine via intravenous infusion in a timeframe of about 90 min. One day before her death a befriended notary of the couple visited Dora V. and obtained a blank signature. After her death, a will was forged using this signature, rendering the couple sole heirs of Dora V.'s estate with a value of several million euros. Post-mortem toxicology was performed in three different institutes of legal medicine. The concentrations of pethidine in peripheral venous blood were between 6.1 and 6.5mg/l and 9.5 and 17.2mg/kg in brain. Pharmacokinetic calculation confirms the given dose. There was no doubt that the cause of death was acute pethidine intoxication. The accused couple claimed that this dose of pethidine was indicated to relief pain, and as the pathologists said in their expert opinions that the hiatus hernia could explain her death, the court had to acquit the accused. This very special case demonstrates that preconceived murder of a sick person with suitable analgesics cannot be proven--at least not with the methods available to forensic toxicology and pathology. This has to be taken into consideration if euthanasia will be legalised under special circumstances. PMID:15172078

  7. Impairment of biliverdin reductase-A promotes brain insulin resistance in Alzheimer disease: A new paradigm.

    PubMed

    Barone, Eugenio; Di Domenico, Fabio; Cassano, Tommaso; Arena, Andrea; Tramutola, Antonella; Lavecchia, Michele Angelo; Coccia, Raffaella; Butterfield, D Allan; Perluigi, Marzia

    2016-02-01

    Clinical studies suggest a link between peripheral insulin resistance and cognitive dysfunction. Interestingly, post-mortem analyses of Alzheimer disease (AD) subjects demonstrated insulin resistance in the brain proposing a role for cognitive deficits observed in AD. However, the mechanisms responsible for the onset of brain insulin resistance (BIR) need further elucidations. Biliverdin reductase-A (BVR-A) emerged as a unique Ser/Thr/Tyr kinase directly involved in the insulin signaling and represents an up-stream regulator of the insulin signaling cascade. Because we previously demonstrated the oxidative stress (OS)-induced impairment of BVR-A in human AD brain, we hypothesize that BVR-A dysregulation could be associated with the onset of BIR in AD. In the present work, we longitudinally analyze the age-dependent changes of (i) BVR-A protein levels and activation, (ii) total oxidative stress markers levels (PC, HNE, 3-NT) as well as (iii) IR/IRS1 levels and activation in the hippocampus of the triple transgenic model of AD (3xTg-AD) mice. Furthermore, ad hoc experiments have been performed in SH-SY5Y neuroblastoma cells to clarify the molecular mechanism(s) underlying changes observed in mice. Our results show that OS-induced impairment of BVR-A kinase activity is an early event, which starts prior the accumulation of Aβ and tau pathology or the elevation of TNF-α, and that greatly contribute to the onset of BIR along the progression of AD pathology in 3xTg-Ad mice. Based on these evidence we, therefore, propose a new paradigm for which: OS-induced impairment of BVR-A is firstly responsible for a sustained activation of IRS1, which then causes the stimulation of negative feedback mechanisms (i.e. mTOR) aimed to turn-off IRS1 hyper-activity and thus BIR. Similar alterations characterize also the normal aging process in mice, positing BVR-A impairment as a possible bridge in the transition from normal aging to AD. PMID:26698666

  8. [Post-mortem examination prior to cremation--an instrument to verify the quality of medical post-mortems and uncover non-natural deaths?].

    PubMed

    Germerott, Tanja; Todt, Melanie; Bode-Jänisch, Stefanie; Albrecht, Knut; Breitmeier, Dirk

    2012-01-01

    The external post-mortem examination, its deficient quality and possible causes have been the subject of numerous political and professional discussions. The external post-mortem examination is the basis for the decision whether further criminal investigations are required to clarify the cause of death. It is thus an essential instrument to ensure legal certainty. Before cremation, a second external post-mortem examination is performed by a public medical officer to make sure that errors of the first post-mortem are corrected. In the present study, cases were retrospectively analyzed in which a forensic autopsy had been ordered on the basis of the results of the post-mortem examination performed before cremation. The entries on the death certificate regarding the manner and cause of death were compared with the autopsy results. Between 1998 and 2007, 387 autopsies were ordered after external examination before cremation. In 55 cases (14.2%), the autopsy revealed a non-natural death, although a natural death had been attested on the death certificate. In descending order, a wrong manner of death was attested by clinicians, general practitioners and emergency physicians. With regard to the place where the first external post-mortem had been performed the lowest error rate was seen in nursing homes. Concerning the cause of death, discrepancies between the first post-mortem and autopsy were found in 59.4% of the cases. In this respect, general practitioners and clinicians were ranking first, whereas in nursing homes the cause of death was wrongly assessed in over 70% of cases. At present, the medical post-mortem does not meet the required quality standards, especially with regard to legal certainty. Determination of the cause of death on the basis of the external post-mortem examination is a challenging task even for the experienced medical examiner. As to the categorization of the manner of death it has to be stated that non-natural deaths are often not recognized or

  9. Postmortem diagnosis of diabetes mellitus and its complications

    PubMed Central

    Palmiere, Cristian

    2015-01-01

    Diabetes mellitus has become a major cause of death worldwide and diabetic ketoacidosis is the most common cause of death in children and adolescents with type 1 diabetes. Acute complications of diabetes mellitus as causes of death may be difficult to diagnose due to missing characteristic macroscopic and microscopic findings. Biochemical analyses, including vitreous glucose, blood (or alternative specimen) beta-hydroxybutyrate, and blood glycated hemoglobin determination, may complement postmortem investigations and provide useful information for determining the cause of death even in corpses with advanced decompositional changes. In this article, we performed a review of the literature pertaining to the diagnostic performance of classical and novel biochemical parameters that may be used in the forensic casework to identify disorders in glucose metabolism. We also present a review focusing on the usefulness of traditional and alternative specimens that can be sampled and subsequently analyzed to diagnose acute complications of diabetes mellitus as causes of death. PMID:26088843

  10. The Elusive Universal Post-Mortem Interval Formula

    SciTech Connect

    Vass, Arpad Alexander

    2011-01-01

    The following manuscript details our initial attempt at developing universal post-mortem interval formulas describing human decomposition. These formulas are empirically derived from data collected over the last 20 years from the University of Tennessee's Anthropology Research Facility, in Knoxville, Tennessee, USA. Two formulas were developed (surface decomposition and burial decomposition) based on temperature, moisture, and the partial pressure of oxygen, as being three of the four primary drivers for human decomposition. It is hoped that worldwide application of these formulas to environments and situations not readily studied in Tennessee will result in interdisciplinary cooperation between scientists and law enforcement personnel that will allow for future refinements of these models leading to increased accuracy.

  11. The eyeball killer: serial killings with postmortem globe enucleation.

    PubMed

    Coyle, Julie; Ross, Karen F; Barnard, Jeffrey J; Peacock, Elizabeth; Linch, Charles A; Prahlow, Joseph A

    2015-05-01

    Although serial killings are relatively rare, they can be the cause of a great deal of anxiety while the killer remains at-large. Despite the fact that the motivations for serial killings are typically quite complex, the psychological analysis of a serial killer can provide valuable insight into how and why certain individuals become serial killers. Such knowledge may be instrumental in preventing future serial killings or in solving ongoing cases. In certain serial killings, the various incidents have a variety of similar features. Identification of similarities between separate homicidal incidents is necessary to recognize that a serial killer may be actively killing. In this report, the authors present a group of serial killings involving three prostitutes who were shot to death over a 3-month period. Scene and autopsy findings, including the unusual finding of postmortem enucleation of the eyes, led investigators to recognize the serial nature of the homicides. PMID:25682709

  12. Outdoor post-mortem depredation by local fauna.

    PubMed

    Feola, Alessandro; Campilongo, Sara; Pietra, Bruno Della

    2014-01-01

    We present the case of complete post-mortem decapitation of a 43 years old man killed by gunshots discharged from a distance of 40 - 50 cm. The corpse was left in the courtyard of his isolated carpentry and a mongrel dog lived in that courtyard, maybe attracted by the blood gushed from the wound, got a depredation of the corpse till the complete decapitation and the removal of all intrathoracic organs. The action of the dog was completed by the rats and mice that lived in the place. The case is not rare and sometimes the alteration of the features of the corpse makes it impossible for the investigators, to objectify any other signs of criminal nature. PMID:24625020

  13. Post-mortem findings in a patient with avian influenza A (H5N6) virus infection.

    PubMed

    Gao, R; Pan, M; Li, X; Zou, X; Zhao, X; Li, T; Yang, H; Zou, S; Bo, H; Xu, J; Li, S; Zhang, M; Li, Z; Wang, D; Zaki, S R; Shu, Y

    2016-06-01

    Avian influenza A (H5N6) has been found to infect humans, and has resulted in ten cases with six deaths in China since 2014. Here, we describe the systematic post-mortem pathology of a patient fatally infected with H5N6 virus and evaluate the associated pathogenesis compared with H1N1 pdm09 fatal cases. The most prominent histopathological features were diffuse alveolar damage and pulmonary vasculitis in the lungs of the patient. The virus disseminated to extrapulmonary organs, including the brain. Compared with H1N1 pdm09 fatal infection, H5N6 infection induced a more exacerbated immune response involving overt pulmonary inflammation, which led to alveolar damage and respiratory failure. PMID:27040806

  14. A comparison of direct fluorescent antibody and Giemsa staining for the post-mortem diagnosis of anaplasmosis.

    PubMed

    Johnston, L A; Trueman, K F; Leatch, G; Wilson, A J

    1980-03-01

    Direct fluorescent antibody (DFA) and Giemsa staining of Anaplasma marginale were compared in smears collected serially at post-mortem (PM) from 11 experimentally infected calves. Once smears had been prepared and air-dried they could be held for at least 5 days before staining with either technique with no noticeable change in staining quality. DFA staining was more sensitive in detecting anaplasms in smears than Giemsa staining. Anaplasma spp could be differentiated from Babesia bovis and B. bigemina by DFA staining but there were cross reactions between A. marginale and A. centrale. Blood smears prepared from subcutaneous vessels in the legs provided better diagnostic material than kidney, heart and lung smears. Brain smears were not suitable for PM diagnosis using either staining technique. PMID:7002139

  15. The cardiothoracic ratio on post-mortem computer tomography.

    PubMed

    Jotterand, M; Doenz, F; Grabherr, S; Faouzi, M; Boone, S; Mangin, P; Michaud, K

    2016-09-01

    In clinical practice, the cardiothoracic ratio (CTR) was first utilized on plain chest radiography, and subsequently with computed tomography (CT) to diagnose cardiomegaly with a threshold of 0.5. Using CTR in forensic practice could help to detect cardiomegaly on post-mortem CT (PMCT) prior to the autopsy. However, an adaption of the threshold could be necessary because of post-mortem changes. Our retrospective study aimed to measure the CTR on PMCT and test the possible influence of variables. We selected 109 autopsy cases in which the heart weight was within normal limits. A forensic pathologist and a radiologist measured separately the CTR on axial and scout views on PMCT. We tested the statistical concordance between the two readers and between the axial and scout view and identified factors that could be associated with a modification of the CTR. The CTR measurements revealed an overestimation of the measurements made on scout compared to axial view. The inter-reader correlation was very high for both views. Among the different variables statistically tested, heart dilatation and body mass index (BMI) were the only two factors statistically associated with an augmentation of the CTR. The CTR can be useful in the diagnosis of cardiomegaly on PMCT. However, dilatation of the cardiac chambers caused by acute heart failure may be misinterpreted radiographically as cardiomegaly. Inter-observer reliability in our study was very high. CTR may be overestimated when measured on the scout view. Further investigations with larger cohorts, including cases with cardiac hypertrophy, are necessary to better understand the relationship between radiological CTR and the morphology of the heart. PMID:26886107

  16. Postmortem validation of breast density using dual-energy mammography

    SciTech Connect

    Molloi, Sabee Ducote, Justin L.; Ding, Huanjun; Feig, Stephen A.

    2014-08-15

    Purpose: Mammographic density has been shown to be an indicator of breast cancer risk and also reduces the sensitivity of screening mammography. Currently, there is no accepted standard for measuring breast density. Dual energy mammography has been proposed as a technique for accurate measurement of breast density. The purpose of this study is to validate its accuracy in postmortem breasts and compare it with other existing techniques. Methods: Forty postmortem breasts were imaged using a dual energy mammography system. Glandular and adipose equivalent phantoms of uniform thickness were used to calibrate a dual energy basis decomposition algorithm. Dual energy decomposition was applied after scatter correction to calculate breast density. Breast density was also estimated using radiologist reader assessment, standard histogram thresholding and a fuzzy C-mean algorithm. Chemical analysis was used as the reference standard to assess the accuracy of different techniques to measure breast composition. Results: Breast density measurements using radiologist reader assessment, standard histogram thresholding, fuzzy C-mean algorithm, and dual energy were in good agreement with the measured fibroglandular volume fraction using chemical analysis. The standard error estimates using radiologist reader assessment, standard histogram thresholding, fuzzy C-mean, and dual energy were 9.9%, 8.6%, 7.2%, and 4.7%, respectively. Conclusions: The results indicate that dual energy mammography can be used to accurately measure breast density. The variability in breast density estimation using dual energy mammography was lower than reader assessment rankings, standard histogram thresholding, and fuzzy C-mean algorithm. Improved quantification of breast density is expected to further enhance its utility as a risk factor for breast cancer.

  17. Elevated formic acid concentrations in putrefied post-mortem blood and urine samples.

    PubMed

    Viinamäki, Jenni; Rasanen, Ilpo; Vuori, Erkki; Ojanperä, Ilkka

    2011-05-20

    Formic acid (FA) concentration was measured in post-mortem blood and urine samples as methyl formate using a headspace in-tube extraction gas-chromatography-mass-spectrometry method. A total of 113 cases were analyzed, each including a blood and urine sample fortified with 1% sodium fluoride. The cases were divided into three groups: regular (n=59), putrefied (n=30), and methanol-positive (n=22) cases. There was no evidence of ante-mortem methanol consumption in the regular and putrefied cases. In regular cases, the mean (and median) FA concentrations were 0.04 g/l (0.04 g/l) and 0.06 g/l (0.04 g/l) in blood and urine, respectively. In putrefied cases, the mean (and median) FA concentrations were substantially higher, 0.24 g/l (0.22 g/l) and 0.25 g/l (0.15 g/l) in blood and urine, respectively. In three putrefied cases, FA concentration in blood exceeded 0.5 g/l, a level associated with fatal methanol poisoning. Ten putrefied cases were reanalyzed after 3-4 months storage, and no significant changes in FA concentrations were seen. These observations suggest that FA was formed by putrefaction during the post-mortem period, not during sample storage when sodium fluoride was added as a preservative. In methanol-positive cases, the mean (and median) FA concentrations were 0.80 g/l (0.88 g/l) and 3.4 g/l (3.3 g/l) in blood and urine, respectively, and the concentrations ranged from 0.19 to 1.0 g/l in blood and from 1.7 to 5.6 g/l in urine. The mean (and median) methanol concentrations in methanol-positive cases were 3.0 g/l (3.0 g/l) and 4.4 g/l (4.7 g/l) in blood and in urine, respectively. The highest methanol concentrations were 6.0 g/l and 8.7 g/l in blood and urine, respectively. No ethyl alcohol was found in the methanol-positive blood samples. Poor correlation was shown between blood and urine concentrations of FA. Poor correlations were also shown, in both blood and urine, between methanol and FA concentrations. PMID:21112705

  18. Examining the decomposed brain.

    PubMed

    MacKenzie, James Mackintosh

    2014-12-01

    Examination of the decomposed brain is a largely neglected area of forensic neuropathology. However, careful examination often yields valuable information that may assist in criminal proceedings. Decomposition encompasses the processes of autolysis, putrefaction, and decay. Most decomposed brains will be affected by both autolysis and putrefaction, resulting in a brain that may, at one end of the spectrum, be almost normal or, at the other end, pulpified, depending on the conditions in which the body remained after death and the postmortem interval. Naked eye examination may detect areas of hemorrhage and also guides appropriate sampling for histology. Histological appearances are often better than what would be predicted from the state of the brain. Histology often confirms macroscopic abnormalities and may also reveal other features such as ischemic injury. Silver staining demonstrates neuritic plaques, and immunocytochemistry for β-amyloid precursor protein and other molecules produces results comparable with those seen in well-preserved fixed brains. The usefulness of information derived from the examination of the decomposed brain in criminal proceedings is illustrated with 6 case reports drawn from the author's own practice. PMID:25384305

  19. Pork Quality Traits According to Postmortem pH and Temperature in Berkshire.

    PubMed

    Kim, Tae Wan; Kim, Chul Wook; Yang, Mi Ra; No, Gun Ryoung; Kim, Sam Woong; Kim, Il-Suk

    2016-01-01

    This study was performed to investigate the role of pH and temperature postmortem, and to demonstrate the importance of these factors in determining meat quality. Postmortem pH 45min (pH at 45 min postmortem or initial pH) via analysis of Pearson's correlation showed high positive correlation with pH change pH c24 (pH change from pH 45min to pH 24h postmortem). However, postmortem pH after 24 h (pH 24h or ultimate pH) had a high negative correlation with pH change, pH c24 , CIE L*, and protein content. Initial temperature postmortem (T 1h ) was positively associated with a change in temperature from 45 min to 24 h postmortem (T c24 ) and cooking loss, but negatively correlated with water holding capacity. Temperature at 24 h postmortem (T 24h ) was negatively associated with T c24 . Collectively, these results indicate that higher initial pH was associated with higher pH c24 , T 1h , and T c24 . However, higher initial pH was associated with a reduction in carcass weight, backfat thickness, CIE a* and b*, water holding capacity, collagen and fat content, drip loss, and cooking loss as well as decreased shear force. In contrast, CIE a* and b*, drip loss, cooking loss, and shear force in higher ultimate pH was showed by a similar pattern to higher initial pH, whereas pH c24 , carcass weight, backfat thickness, water holding capacity, fat content, moisture content, protein content, T 1h , T 24h , and T c24 were exhibited by completely differential patterns (p<0.05). Therefore, we suggest that initial pH, ultimate pH, and temperatures postmortem are important factors in determining the meat quality of pork. PMID:27499661

  20. Fluorescently labeled bacteria provide insight on post-mortem microbial transmigration.

    PubMed

    Burcham, Z M; Hood, J A; Pechal, J L; Krausz, K L; Bose, J L; Schmidt, C J; Benbow, M E; Jordan, H R

    2016-07-01

    Microbially mediated mechanisms of human decomposition begin immediately after death, and are a driving force for the conversion of a once living organism to a resource of energy and nutrients. Little is known about post-mortem microbiology in cadavers, particularly the community structure of microflora residing within the cadaver and the dynamics of these communities during decomposition. Recent work suggests these bacterial communities undergo taxa turnover and shifts in community composition throughout the post-mortem interval. In this paper we describe how the microbiome of a living host changes and transmigrates within the body after death thus linking the microbiome of a living individual to post-mortem microbiome changes. These differences in the human post-mortem from the ante-mortem microbiome have demonstrated promise as evidence in death investigations. We investigated the post-mortem structure and function dynamics of Staphylococcus aureus and Clostridium perfringens after intranasal inoculation in the animal model Mus musculus L. (mouse) to identify how transmigration of bacterial species can potentially aid in post-mortem interval estimations. S. aureus was tracked using in vivo and in vitro imaging to determine colonization routes associated with different physiological events of host decomposition, while C. perfringens was tracked using culture-based techniques. Samples were collected at discrete time intervals associated with various physiological events and host decomposition beginning at 1h and ending at 60 days post-mortem. Results suggest that S. aureus reaches its highest concentration at 5-7 days post-mortem then begins to rapidly decrease and is undetectable by culture on day 30. The ability to track these organisms as they move in to once considered sterile space may be useful for sampling during autopsy to aid in determining post-mortem interval range estimations, cause of death, and origins associated with the geographic location of human

  1. Pork Quality Traits According to Postmortem pH and Temperature in Berkshire

    PubMed Central

    Kim, Tae Wan; Kim, Chul Wook; Yang, Mi Ra; No, Gun Ryoung; Kim, Il-Suk

    2016-01-01

    This study was performed to investigate the role of pH and temperature postmortem, and to demonstrate the importance of these factors in determining meat quality. Postmortem pH45min (pH at 45 min postmortem or initial pH) via analysis of Pearson’s correlation showed high positive correlation with pH change pHc24 (pH change from pH45min to pH24h postmortem). However, postmortem pH after 24 h (pH24h or ultimate pH) had a high negative correlation with pH change, pHc24, CIE L*, and protein content. Initial temperature postmortem (T1h ) was positively associated with a change in temperature from 45 min to 24 h postmortem (Tc24) and cooking loss, but negatively correlated with water holding capacity. Temperature at 24 h postmortem (T24h) was negatively associated with Tc24. Collectively, these results indicate that higher initial pH was associated with higher pHc24, T1h, and Tc24. However, higher initial pH was associated with a reduction in carcass weight, backfat thickness, CIE a* and b*, water holding capacity, collagen and fat content, drip loss, and cooking loss as well as decreased shear force. In contrast, CIE a* and b*, drip loss, cooking loss, and shear force in higher ultimate pH was showed by a similar pattern to higher initial pH, whereas pHc24, carcass weight, backfat thickness, water holding capacity, fat content, moisture content, protein content, T1h, T24h, and Tc24 were exhibited by completely differential patterns (p<0.05). Therefore, we suggest that initial pH, ultimate pH, and temperatures postmortem are important factors in determining the meat quality of pork. PMID:27499661

  2. Smeared antibranes polarise in AdS

    NASA Astrophysics Data System (ADS)

    Gautason, Fridrik Freyr; Truijen, Brecht; Van Riet, Thomas

    2015-07-01

    In the recent literature it has been questioned whether the local backreaction of antibranes in flux throats can induce a perturbative brane-flux decay. Most evidence for this can be gathered for D6 branes and D p branes smeared over 6 - p compact directions, in line with the absence of finite temperature solutions for these cases. The solutions in the literature have flat worldvolume geometries and non-compact transversal spaces. In this paper we consider what happens when the worldvolume is AdS and the transversal space is compact. We show that in these circumstances brane polarisation smoothens out the flux singularity, which is an indication that brane-flux decay is prevented. This is consistent with the fact that the cosmological constant would be less negative after brane-flux decay. Our results extend recent results on AdS7 solutions from D6 branes to AdS p+1 solutions from D p branes. We show that supersymmetry of the AdS solutions depend on p non-trivially.

  3. Molecular systems evaluation of oligomerogenic APPE693Q and fibrillogenic APPKM670/671NL/PSEN1Δexon9 mouse models identifies shared molecular features with human Alzheimer’s brain molecular pathology

    PubMed Central

    Readhead, Ben; Haure-Mirande, Jean-Vianney; Zhang, Bin; Haroutunian, Vahram; Gandy, Sam; Schadt, Eric E.; Dudley, Joel T.; Ehrlich, Michelle E.

    2016-01-01

    Identification and characterization of molecular mechanisms that connect genetic risk factors to initiation and evolution of disease pathophysiology represent major goals and opportunities for improving therapeutic and diagnostic outcomes in Alzheimer’s disease (AD). Integrative genomic analysis of the human AD brain transcriptome holds potential for revealing novel mechanisms of dysfunction that underlie the onset and/or progression of the disease. We performed an integrative genomic analysis of brain tissue derived transcriptomes measured from two lines of mice expressing distinct mutant AD-related proteins. The first line expresses oligomerogenic mutant APPE693Q inside neurons, leading to accumulation of amyloid beta (Aβ) oligomers and behavioral impairment, but never develops parenchymal fibrillar amyloid deposits. The second line expresses APPKM670/671NL/PSEN1Δexon9 in neurons and accumulates fibrillar Aβ amyloid and amyloid plaques accompanied by neuritic dystrophy and behavioral impairment. We performed RNA-sequencing analyses of dentate gyrus and entorhinal cortex from each line and from wild type mice. We then performed an integrative genomic analysis to identify dysregulated molecules and pathways, comparing transgenic mice with wild type controls as well as to each other. We also compared these results with datasets derived from human AD brain. Differential gene and exon expression analysis revealed pervasive alterations in APP/Aβ metabolism, epigenetic control of neurogenesis, cytoskeletal organization, and extracellular matrix regulation. Comparative molecular analysis converged on FMR1 (Fragile X Mental Retardation-1), an important negative regulator of APP translation and oligomerogenesis in the post-synaptic space. Integration of these transcriptomic results with human postmortem AD gene networks, differential expression and differential splicing signatures identified significant similarities in pathway dysregulation, including extracellular

  4. Molecular systems evaluation of oligomerogenic APP(E693Q) and fibrillogenic APP(KM670/671NL)/PSEN1(Δexon9) mouse models identifies shared features with human Alzheimer's brain molecular pathology.

    PubMed

    Readhead, B; Haure-Mirande, J-V; Zhang, B; Haroutunian, V; Gandy, S; Schadt, E E; Dudley, J T; Ehrlich, M E

    2016-08-01

    Identification and characterization of molecular mechanisms that connect genetic risk factors to initiation and evolution of disease pathophysiology represent major goals and opportunities for improving therapeutic and diagnostic outcomes in Alzheimer's disease (AD). Integrative genomic analysis of the human AD brain transcriptome holds potential for revealing novel mechanisms of dysfunction that underlie the onset and/or progression of the disease. We performed an integrative genomic analysis of brain tissue-derived transcriptomes measured from two lines of mice expressing distinct mutant AD-related proteins. The first line expresses oligomerogenic mutant APP(E693Q) inside neurons, leading to the accumulation of amyloid beta (Aβ) oligomers and behavioral impairment, but never develops parenchymal fibrillar amyloid deposits. The second line expresses APP(KM670/671NL)/PSEN1(Δexon9) in neurons and accumulates fibrillar Aβ amyloid and amyloid plaques accompanied by neuritic dystrophy and behavioral impairment. We performed RNA sequencing analyses of the dentate gyrus and entorhinal cortex from each line and from wild-type mice. We then performed an integrative genomic analysis to identify dysregulated molecules and pathways, comparing transgenic mice with wild-type controls as well as to each other. We also compared these results with datasets derived from human AD brain. Differential gene and exon expression analysis revealed pervasive alterations in APP/Aβ metabolism, epigenetic control of neurogenesis, cytoskeletal organization and extracellular matrix (ECM) regulation. Comparative molecular analysis converged on FMR1 (Fragile X Mental Retardation 1), an important negative regulator of APP translation and oligomerogenesis in the post-synaptic space. Integration of these transcriptomic results with human postmortem AD gene networks, differential expression and differential splicing signatures identified significant similarities in pathway dysregulation

  5. AdS orbifolds and Penrose limits

    SciTech Connect

    Alishahiha, Mohsen; Sheikh-Jabbari, Mohammad M.; Tatar, Radu

    2002-12-09

    In this paper we study the Penrose limit of AdS{sub 5} orbifolds. The orbifold can be either in the pure spatial directions or space and time directions. For the AdS{sub 5}/{Lambda} x S{sup 5} spatial orbifold we observe that after the Penrose limit we obtain the same result as the Penrose limit of AdS{sub 5} x S{sup 5}/{Lambda}. We identify the corresponding BMN operators in terms of operators of the gauge theory on R x S{sup 3}/{Lambda}. The semi-classical description of rotating strings in these backgrounds have also been studied. For the spatial AdS orbifold we show that in the quadratic order the obtained action for the fluctuations is the same as that in S{sup 5} orbifold, however, the higher loop correction can distinguish between two cases.

  6. Alzheimer disease (AD) specific transcription, DNA methylation and splicing in twenty AD associated loci

    PubMed Central

    Humphries, Crystal; Kohli, Martin A.; Whitehead, Patrice; Mash, Deborah C.; Pericak-Vance, Margaret A.; Gilbert, John

    2015-01-01

    Genome-wide association studies have identified twenty loci associated with late-onset Alzheimer disease (LOAD). We examined each of the twenty loci, specifically the ±50kb region surrounding the most strongly associated variant, for changes in gene(s) transcription specific to LOAD. Post-mortem human brain samples were examined for expression, methylation, and splicing differences. LOAD specific differences were detected by comparing LOAD to normal and “disease” controls. Eight loci, prominently ABCA7, contain LOAD specific differences. Significant changes in the CELF1 and ZCWPW1 loci occurred in genes not located nearest the associated variant, suggesting that these genes should be investigated further as LOAD candidates. PMID:26004081

  7. Biochemistry of postmortem muscle - lessons on mechanisms of meat tenderization.

    PubMed

    Huff Lonergan, Elisabeth; Zhang, Wangang; Lonergan, Steven M

    2010-09-01

    It is certain that meat tenderness is a highly valued consumer trait and thus definition of the multiple processes that influence meat tenderness will provide clues toward improving meat quality and value. The natural process by which meat becomes tender is complex. Tenderness development is dependent on the architecture and the integrity of the skeletal muscle cell and on events that modify those proteins and their interaction. Specifically protein degradation and protein oxidation have been identified as processes that modify proteins as well as the tenderness of meat. The intracellular environment is a major factor that controls these events. Ultimately, the interplay between these events determines the rate and extent of tenderization. Given the intricacy of the structure of the muscle cell, coupled with the complexity of the regulation of protein modification and the ever-changing intracellular environment it is not surprising that this area of research is a very dynamic field. Just as the overall integrity and function of muscle cells does not depend on a single protein, but rather on the coordinated interaction of several proteins, the structural weakening of muscle cells during postmortem aging also must not depend on the degradation of a single myofibrillar or other cytoskeletal protein. The proteins mentioned in this review are located in different regions of the muscle cell, and most have been implicated in some manner as being important in maintaining the structure and function of the muscle cell. Oxidation of myosin heavy chain, a predominant protein in the myofibril, is known to promote aggregation and toughening of meat. Degradation of proteins such as desmin, filamin, dystrophin, and talin (all located at the periphery of the Z-line) may disrupt the lateral register and integrity of the myofibril themselves as well as the attachments of the peripheral layer of myofibril to the sarcolemma. Degradation of the proteins within the myofibril that are

  8. Herpes simplex encephalitis is linked with selective mitochondrial damage; a post-mortem and in vitro study.

    PubMed

    Wnęk, Małgorzata; Ressel, Lorenzo; Ricci, Emanuele; Rodriguez-Martinez, Carmen; Guerrero, Julio Cesar Villalvazo; Ismail, Zarini; Smith, Colin; Kipar, Anja; Sodeik, Beate; Chinnery, Patrick F; Solomon, Tom; Griffiths, Michael J

    2016-09-01

    Herpes simplex virus type-1 (HSV-1) encephalitis (HSE) is the most commonly diagnosed cause of viral encephalitis in western countries. Despite antiviral treatment, HSE remains a devastating disease with high morbidity and mortality. Improved understanding of pathogenesis may lead to more effective therapies. Mitochondrial damage has been reported during HSV infection in vitro. However, whether it occurs in the human brain and whether this contributes to the pathogenesis has not been fully explored. Minocycline, an antibiotic, has been reported to protect mitochondria and limit brain damage. Minocycline has not been studied in HSV infection. In the first genome-wide transcriptomic study of post-mortem human HSE brain tissue, we demonstrated a highly preferential reduction in mitochondrial genome (MtDNA) encoded transcripts in HSE cases (n = 3) compared to controls (n = 5). Brain tissue exhibited a significant inverse correlation for immunostaining between cytochrome c oxidase subunit 1 (CO1), a MtDNA encoded enzyme subunit, and HSV-1; with lower abundance for mitochondrial protein in regions where HSV-1 was abundant. Preferential loss of mitochondrial function, among MtDNA encoded components, was confirmed using an in vitro primary human astrocyte HSV-1 infection model. Dysfunction of cytochrome c oxidase (CO), a mitochondrial enzyme composed predominantly of MtDNA encoded subunits, preceded that of succinate dehydrogenase (composed entirely of nuclear encoded subunits). Minocycline treated astrocytes exhibited higher CO1 transcript abundance, sustained CO activity and cell viability compared to non-treated astrocytes. Based on observations from HSE patient tissue, this study highlights mitochondrial damage as a critical and early event during HSV-1 infection. We demonstrate minocycline preserves mitochondrial function and cell viability during HSV-1 infection. Minocycline, and mitochondrial protection, offers a novel adjunctive therapeutic approach for

  9. Popliteal Vein Blood Sampling and the Postmortem Redistribution of Diazepam, Methadone, and Morphine.

    PubMed

    Lemaire, Eric; Schmidt, Carl; Denooz, Raphael; Charlier, Corinne; Boxho, Philippe

    2016-07-01

    Postmortem redistribution (PMR) refers to the site- and time-related blood drug concentration variations after death. We compared central blood (cardiac and subclavian) with peripheral blood (femoral and popliteal) concentrations of diazepam, methadone, and morphine. To our knowledge, popliteal blood has never been compared with other sites. Intracardiac blood (ICB), subclavian blood (SB), femoral blood (FB), and popliteal blood (PB) were sampled in 30 cases. To assess PMR, mean concentrations and ratios were compared. Influence of postmortem interval on mean ratios was also assessed. Results show that popliteal mean concentrations were lower than those for other sites for all three drugs, even lower than femoral blood; mean ratios suggested that the popliteal site was less subject to PMR, and estimated postmortem interval did not influence ratios except for diazepam and methadone FB/PB. In conclusion, our study is the first to explore the popliteal site and suggests that popliteal blood is less prone to postmortem redistribution. PMID:27364283

  10. Postmortem computed tomography (PMCT) and disaster victim identification.

    PubMed

    Brough, A L; Morgan, B; Rutty, G N

    2015-09-01

    Radiography has been used for identification since 1927, and established a role in mass fatality investigations in 1949. More recently, postmortem computed tomography (PMCT) has been used for disaster victim identification (DVI). PMCT offers several advantages compared with fluoroscopy, plain film and dental X-rays, including: speed, reducing the number of on-site personnel and imaging modalities required, making it potentially more efficient. However, there are limitations that inhibit the international adoption of PMCT into routine practice. One particular problem is that due to the fact that forensic radiology is a relatively new sub-speciality, there are no internationally established standards for image acquisition, image interpretation and archiving. This is reflected by the current INTERPOL DVI form, which does not contain a PMCT section. The DVI working group of the International Society of Forensic Radiology and Imaging supports the use of imaging in mass fatality response and has published positional statements in this area. This review will discuss forensic radiology, PMCT, and its role in disaster victim identification. PMID:26108152

  11. [Detection of dengue virus antigen in post-mortem tissues].

    PubMed

    Rivera, Jorge; Neira, Marcela; Parra, Edgar; Méndez, Jairo; Sarmiento, Ladys; Caldas, María Leonor

    2014-01-01

    The epidemiological situation of dengue has worsened over the last decade. The difficulties in preventing its transmission and the absence of a vaccine or specific treatment have made dengue a serious risk to public health, health centers and research systems at different levels. Currently, most studies on the pathogenesis of dengue infection focus on the T-cell immune response almost exclusively in secondary infections and are aimed at identifying the mechanisms involved in the development of vascular permeability and bleeding events that accompany the infection. This report describes the case of a baby girl less than 45 days of age with clinical signs of severe dengue, whose diagnosis was confirmed by reverse transcription polymerase chain reaction in post-mortem tissue samples and by the ancillary diagnostic use of immunohistochemistry, which detected viral antigens in all organs obtained at autopsy. This case highlights the importance of studying primary infections associated with severe dengue, particularly in children, who are more likely to develop the severe form of the disease without previous infection, and it further stresses the importance of a diagnosis that should not be based solely on the examination of liver tissue samples when studying the pathogenesis of the viral infection. PMID:25504239

  12. An acute gabapentin fatality: a case report with postmortem concentrations.

    PubMed

    Cantrell, F Lee; Mena, Othon; Gary, Ray D; McIntyre, Iain M

    2015-07-01

    Gabapentin (GBP) (Neurontin®, Horizant®, Gralise®) is a widely prescribed medication used primarily for the treatment of epilepsy and neuropathic pain. GBP has a favorable adverse effect profile in therapeutic dosing with the most common reported effects being dizziness, fatigue, drowsiness, weight gain, and peripheral edema. Even with intentional GBP self-poisonings, serious effects are rare. A 47-year-old female was found dead at work with her daughter's bottle of GBP 600 mg. There were 26 tablets missing and the decedent's only known medication was hydrocodone/acetaminophen. Following initial detection by an alkaline drug screen (GC-MS), analysis utilizing specific liquid chromatography-mass spectrometry revealed an elevated postmortem GBP peripheral blood concentration of 37 mg/L, central blood 32 mg/L, liver 26 mg/kg, vitreous 32 mg/L, and gastric contents 6 mg. Screening for volatiles, drugs of abuse, alkaline compounds, and acid/neutral compounds was negative with the exception of ibuprofen (<2 mg/L) detected in peripheral blood. This report presents a fatality that appears to be associated with an isolated and acute GBP ingestion. PMID:25904080

  13. Disaster victim identification: new applications for postmortem computed tomography.

    PubMed

    Blau, Soren; Robertson, Shelley; Johnstone, Marnie

    2008-07-01

    Mass fatalities can present the forensic anthropologist and forensic pathologist with a different set of challenges to those presented by a single fatality. To date radiography has played an important role in the disaster victim identification (DVI) process. The aim of this paper is to highlight the benefits of applying computed tomography (CT) technology to the DVI process. The paper begins by reviewing the extent to which sophisticated imaging techniques, specifically CT, have been increasingly used to assist in the analysis of deceased individuals. A small scale case study is then presented which describes aspects of the DVI process following a recent Australian aviation disaster involving two individuals. Having grided the scene of the disaster, a total of 41 bags of heavily disrupted human remains were collected. A postmortem examination was subsequently undertaken. Analysis of the CT images of all body parts (n = 162) made it possible not only to identify and side differentially preserved skeletal elements which were anatomically unrecognizable in the heavily disrupted body masses, but also to observe and record useful identifying features such as surgical implants. In this case the role of the forensic anthropologist and CT technology were paramount in facilitating a quick identification, and subsequently, an effective and timely reconciliation, of body parts. Although this case study is small scale, it illustrates the enormous potential for CT imaging to complement the existing DVI process. PMID:18547358

  14. Histological assessment of cellular changes in postmortem gingival specimens for estimation of time since death.

    PubMed

    Yadav, Achla Bharti; Angadi, Punnya V; Kale, Alka D; Yadav, Sumit Kumar

    2015-07-01

    Estimating the time after death is an important aspect of the role of a forensic expert. After death, the body undergoes substantial changes in its chemical and physical composition which can prove useful in providing an indication of the post-mortem interval. The most accurate estimate of the time of death is best achieved early in the post-mortem interval before the many environmental variables are able to affect the result. Whilst dependence on macroscopic observations was the foundation of the past practice, the application of histological techniques is proving to be an increasingly valuable tool in forensic research. The present study was conducted to evaluate the histologic post-mortem changes that take place in human gingival tissues and to correlate these changes with the time interval after death. Thirty one samples of post-mortem human gingival tissues were obtained from a pool of decedents at varied post-mortem intervals (0-8 hrs, 8-16 hrs, 16-24 hrs). Ante-mortem samples of gingival tissues for comparison were obtained from patients undergoing crown lengthening procedure. Histological changes in the epithelium (cytoplasmic and nuclear) and connective tissue were assessed. The initial epithelial changes observed were homogenization and eosinophilia while cytoplasmic vacuolation and other alterations, including shredding of the epithelium, ballooning, loss of nuclei and suprabasilar split were noticed in late post-mortem interval (16-24 hrs). Nuclear changes such as vacuolation, karyorrhexis, pyknosis and karyolysis became increasingly apparent with lengthening post-mortem intervals. Homogenizations of collagen and fibroblast vacuolation were also observed. To conclude; the initiation of decomposition at cellular level appeared within 24 hours of death and other features of decomposition were observed subsequently. Against this background, histological changes in the gingival tissues may be useful in estimating the time of death in the early post-mortem

  15. Adverse events, toxicity and post-mortem data on duloxetine: case reports and literature survey.

    PubMed

    Vey, Eric L; Kovelman, Inna

    2010-05-01

    Duloxetine, a dual acting norepinephrine serotonin reuptake inhibitor, is a relatively new pharmacologic agent utilized in the treatment of depression, as well as diabetic neuropathic pain, fibromyalgia, and female stress urinary incontinence. This expanding scope of usage will inevitably lead to its eventual appearance during routine post-mortem toxicologic assays. Currently there is a paucity of post-mortem toxicologic data concerning duloxetine. The current report provides six additional case reports of post-mortem duloxetine levels, along with a review of duloxetine's pharmacokinetics, and the toxicologic manifestations which have been reported in the literature. The post-mortem levels reported, including the highest level recorded to date, are integrated with previously published reports to generate a foundation for a nascent guide to the interpretation of post-mortem duloxetine levels that could be encountered during routine post-mortem toxicologic analyses, and establish a basis upon which the establishment of toxic and lethal thresholds for this compound can be further elucidated with greater clarity. PMID:20382351

  16. Running a postmortem service--a business case and clinical experience.

    PubMed

    Cohen, Marta C; Whitby, Elspeth; Fink, Michelle A; Collett, Jacquelene M; Offiah, Amaka C

    2015-04-01

    The purpose of the postmortem examination is to offer answers to explain the cause and manner of death. In the case of perinatal, infant and paediatric postmortem examinations, the goal is to identify unsuspected associated features, to describe pathogenic mechanisms and new conditions, and to evaluate the clinical management and diagnosis. Additionally, the postmortem examination is useful to counsel families regarding the probability of recurrence in future pregnancies and to inform family planning. Worldwide the rate of paediatric autopsy examinations has significantly declined during the last few decades. Religious objections to postmortem dissection and organ retention scandals in the United Kingdom provided some of the impetus for a search for non-invasive alternatives to the traditional autopsy; however, until recently, imaging studies remained an adjunct to, rather than a replacement for, the traditional autopsy. In 2012, Sheffield Children's Hospital National Health Service Foundation Trust set up the service provision of minimally invasive fetal, perinatal and neonatal autopsy, while a postmortem imaging service has been running in Melbourne, Australia, since 2008. Here we summarise the essentials of a business case and practical British and Australian experiences in terms of the pathological and radiologic aspects of setting up a minimally invasive clinical service in the United Kingdom and of developing a clinical postmortem imaging service as a complementary tool to the traditional autopsy in Australia. PMID:25828353

  17. Breast tissue decomposition with spectral distortion correction: A postmortem study

    PubMed Central

    Ding, Huanjun; Zhao, Bo; Baturin, Pavlo; Behroozi, Farnaz; Molloi, Sabee

    2014-01-01

    Purpose: To investigate the feasibility of an accurate measurement of water, lipid, and protein composition of breast tissue using a photon-counting spectral computed tomography (CT) with spectral distortion corrections. Methods: Thirty-eight postmortem breasts were imaged with a cadmium-zinc-telluride-based photon-counting spectral CT system at 100 kV. The energy-resolving capability of the photon-counting detector was used to separate photons into low and high energy bins with a splitting energy of 42 keV. The estimated mean glandular dose for each breast ranged from 1.8 to 2.2 mGy. Two spectral distortion correction techniques were implemented, respectively, on the raw images to correct the nonlinear detector response due to pulse pileup and charge-sharing artifacts. Dual energy decomposition was then used to characterize each breast in terms of water, lipid, and protein content. In the meantime, the breasts were chemically decomposed into their respective water, lipid, and protein components to provide a gold standard for comparison with dual energy decomposition results. Results: The accuracy of the tissue compositional measurement with spectral CT was determined by comparing to the reference standard from chemical analysis. The averaged root-mean-square error in percentage composition was reduced from 15.5% to 2.8% after spectral distortion corrections. Conclusions: The results indicate that spectral CT can be used to quantify the water, lipid, and protein content in breast tissue. The accuracy of the compositional analysis depends on the applied spectral distortion correction technique. PMID:25281953

  18. Breast tissue decomposition with spectral distortion correction: A postmortem study

    SciTech Connect

    Ding, Huanjun; Zhao, Bo; Baturin, Pavlo; Behroozi, Farnaz; Molloi, Sabee

    2014-10-15

    Purpose: To investigate the feasibility of an accurate measurement of water, lipid, and protein composition of breast tissue using a photon-counting spectral computed tomography (CT) with spectral distortion corrections. Methods: Thirty-eight postmortem breasts were imaged with a cadmium-zinc-telluride-based photon-counting spectral CT system at 100 kV. The energy-resolving capability of the photon-counting detector was used to separate photons into low and high energy bins with a splitting energy of 42 keV. The estimated mean glandular dose for each breast ranged from 1.8 to 2.2 mGy. Two spectral distortion correction techniques were implemented, respectively, on the raw images to correct the nonlinear detector response due to pulse pileup and charge-sharing artifacts. Dual energy decomposition was then used to characterize each breast in terms of water, lipid, and protein content. In the meantime, the breasts were chemically decomposed into their respective water, lipid, and protein components to provide a gold standard for comparison with dual energy decomposition results. Results: The accuracy of the tissue compositional measurement with spectral CT was determined by comparing to the reference standard from chemical analysis. The averaged root-mean-square error in percentage composition was reduced from 15.5% to 2.8% after spectral distortion corrections. Conclusions: The results indicate that spectral CT can be used to quantify the water, lipid, and protein content in breast tissue. The accuracy of the compositional analysis depends on the applied spectral distortion correction technique.

  19. Evidential value of postmortem MRI in forensic pathology

    NASA Astrophysics Data System (ADS)

    Schweitzer, Wolf; Schaepman, Michael E.; Ith, Michael; Bruegger, Karin; Thali, Michael J.; Doernhofer, Tanya; Tiefenthaler, Kathrin; Scheurer, Eva; Vock, Peter; Boesch, Chris; Dirnhofer, Richard

    2001-05-01

    We currently evaluate MRI as add-on to dissection. Cases can only build on high evidential values of morphological findings as estimated using Bayesian likelihood-ratios. These values may vary among different cases depending on the quality of the morphology and the discrete hypotheses to be discerned. After scanning 20 bodies using MRI admitted to our institute for autopsy, we reconstructed selected imaging findings from a couple of illustrative cases according to a geometrical model ('Pink Box') designed as an object oriented bridging protocol to enable comparison of autopsy and MRI data. Although it appears obvious that 'three-dimensional imaging yields relevant diagnoses,' comparison of selected findings suggests, that the real evidential value of a postmortem scan depends on basic geometrical features of tissue structures examined. (1) Tissue surfaces are difficult to examine in MRI, including surface features of contact wounds in firearm injuries, lacerations of the pleura, or skin needle marks. (2) Specificity and sensitivity of solid tissue block data depend on contrast and resolution. (3) Tunnels or tubes, such as coronary arteries, linear wound tracks or the aorta offer more degrees of freedom for reconstruction, including spatial reconstruction or cross sectioning in different directions. (4) Three-dimensional rendering of complex objects results in spectacular images. Their evidential value is dependent on the way thresholding of 2D slices is validated. We present illustrative examples which suggest that a possible integration of non-invasive imaging methods into Forensic Pathology in fact need to take basic geometry into consideration when discussing evidential value.

  20. The AdS particle [rapid communication

    NASA Astrophysics Data System (ADS)

    Ghosh, Subir

    2005-09-01

    In this Letter we have considered a relativistic Nambu-Goto model for a particle in AdS metric. With appropriate gauge choice to fix the reparameterization invariance, we recover the previously discussed [S. Ghosh, P. Pal, Phys. Lett. B 618 (2005) 243, arxiv:hep-th/0502192] "exotic oscillator". The Snyder algebra and subsequently the κ-Minkowski spacetime are also derived. Lastly we comment on the impossibility of constructing a non-commutative spacetime in the context of open string where only a curved target space is introduced.

  1. Deuterium inventory in Tore Supra: reconciling particle balance and post-mortem analysis

    NASA Astrophysics Data System (ADS)

    Tsitrone, E.; Brosset, C.; Pégourié, B.; Gauthier, E.; Bouvet, J.; Bucalossi, J.; Carpentier, S.; Corre, Y.; Delchambre, E.; Desgranges, L.; Dittmar, T.; Douai, D.; Ekedahl, A.; Escarguel, A.; Ghendrih, Ph.; Grisolia, C.; Grosman, A.; Gunn, J.; Hong, S. H.; Jacob, W.; Kazarian, F.; Kocan, M.; Khodja, H.; Linez, F.; Loarer, T.; Marandet, Y.; Martinez, A.; Mayer, M.; Meyer, O.; Monier Garbet, P.; Moreau, P.; Pascal, J. Y.; Pasquet, B.; Rimini, F.; Roche, H.; Roure, I.; Rosanvallon, S.; Roubin, P.; Roth, J.; Saint-Laurent, F.; Samaille, F.; Vartanian, S.

    2009-07-01

    Fuel retention, a crucial issue for next step devices, is assessed in present-day tokamaks using two methods: particle balance performed during shots and post-mortem analysis carried out during shutdowns between experimental campaigns. Post-mortem analysis generally gives lower estimates of fuel retention than integrated particle balance. In order to understand the discrepancy between these two methods, a dedicated experimental campaign has been performed in Tore Supra to load the vessel walls with deuterium (D) and monitor the trapped D inventory through particle balance. The campaign was followed by an extensive post-mortem analysis phase of the Tore Supra limiter. This paper presents the status of the analysis phase, including the assessment of the D content in the castellated tile structure of the limiter. Indeed, using combined surface analysis techniques, it was possible to derive the relative contributions of different zones of interest on the limiter (erosion, thick deposits, thin deposits), showing that the post-mortem inventory is mainly due to codeposition (90% of the total), in particular due to gap deposits. However, deuterium was also evidenced deep into the material in erosion zones (10% of the total). At the present stage of the analysis, 50% of the inventory deduced from particle balance has been found through post-mortem analysis, a significant progress with respect to previous studies (factor 8-10 discrepancy). This shows that post-mortem analysis can be consistent with particle balance provided specific procedures are implemented (dedicated campaign followed by extensive post-mortem analysis). Both techniques are needed for a reliable assessment of fuel retention in tokamaks, giving complementary information on how much and where fuel is retained in the vessel walls.

  2. Post-mortem assessment of hypoperfusion of cerebral cortex in Alzheimer's disease and vascular dementia.

    PubMed

    Thomas, Taya; Miners, Scott; Love, Seth

    2015-04-01

    Perfusion is reduced in the cerebral neocortex in Alzheimer's disease. We have explored some of the mechanisms, by measurement of perfusion-sensitive and disease-related proteins in post-mortem tissue from Alzheimer's disease, vascular dementia and age-matched control brains. To distinguish physiological from pathological reduction in perfusion (i.e. reduction exceeding the decline in metabolic demand), we measured the concentration of vascular endothelial growth factor (VEGF), a protein induced under conditions of tissue hypoxia through the actions of hypoxia-inducible factors, and the myelin associated glycoprotein to proteolipid protein 1 (MAG:PLP1) ratio, which declines in chronically hypoperfused brain tissue. To evaluate possible mechanisms of hypoperfusion, we also measured the levels of amyloid-β40, amyloid-β42, von Willebrand factor (VWF; a measure of microvascular density) and the potent vasoconstrictor endothelin 1 (EDN1); we assayed the activity of angiotensin I converting enzyme (ACE), which catalyses the production of another potent vasoconstrictor, angiotensin II; and we scored the severity of arteriolosclerotic small vessel disease and cerebral amyloid angiopathy, and determined the Braak tangle stage. VEGF was markedly increased in frontal and parahippocampal cortex in Alzheimer's disease but only slightly and not significantly in vascular dementia. In frontal cortex the MAG:PLP1 ratio was significantly reduced in Alzheimer's disease and even more so in vascular dementia. VEGF but not MAG:PLP1 increased with Alzheimer's disease severity, as measured by Braak tangle stage, and correlated with amyloid-β42 and amyloid-β42: amyloid-β40 but not amyloid-β40. Although MAG:PLP1 tended to be lowest in cortex from patients with severe small vessel disease or cerebral amyloid angiopathy, neither VEGF nor MAG:PLP1 correlated significantly with the severity of structural vascular pathology (small vessel disease, cerebral amyloid angiopathy or VWF

  3. Probing crunching AdS cosmologies

    NASA Astrophysics Data System (ADS)

    Kumar, S. Prem; Vaganov, Vladislav

    2016-02-01

    Holographic gravity duals of deformations of CFTs formulated on de Sitter spacetime contain FRW geometries behind a horizon, with cosmological big crunch singularities. Using a specific analytically tractable solution within a particular single scalar truncation of {N}=8 supergravity on AdS4, we first probe such crunching cosmologies with spacelike radial geodesics that compute spatially antipodal correlators of large dimension boundary operators. At late times, the geodesics lie on the FRW slice of maximal expansion behind the horizon. The late time two-point functions factorise, and when transformed to the Einstein static universe, they exhibit a temporal non-analyticity determined by the maximal value of the scale factor ã max. Radial geodesics connecting antipodal points necessarily have de Sitter energy Ɛ ≲ ã max, while geodesics with Ɛ > ã max terminate at the crunch, the two categories of geodesics being separated by the maximal expansion slice. The spacelike crunch singularity is curved "outward" in the Penrose diagram for the deformed AdS backgrounds, and thus geodesic limits of the antipodal correlators do not directly probe the crunch. Beyond the geodesic limit, we point out that the scalar wave equation, analytically continued into the FRW patch, has a potential which is singular at the crunch along with complex WKB turning points in the vicinity of the FRW crunch. We then argue that the frequency space Green's function has a branch point determined by ã max which corresponds to the lowest quasinormal frequency.

  4. Consensus brain-derived protein, extraction protocol for the study of human and murine brain proteome using both 2D-DIGE and mini 2DE immunoblotting.

    PubMed

    Fernandez-Gomez, Francisco-Jose; Jumeau, Fanny; Derisbourg, Maxime; Burnouf, Sylvie; Tran, Hélène; Eddarkaoui, Sabiha; Obriot, Hélène; Dutoit-Lefevre, Virginie; Deramecourt, Vincent; Mitchell, Valérie; Lefranc, Didier; Hamdane, Malika; Blum, David; Buée, Luc; Buée-Scherrer, Valérie; Sergeant, Nicolas

    2014-01-01

    Two-dimensional gel electrophoresis (2DE) is a powerful tool to uncover proteome modifications potentially related to different physiological or pathological conditions. Basically, this technique is based on the separation of proteins according to their isoelectric point in a first step, and secondly according to their molecular weights by SDS polyacrylamide gel electrophoresis (SDS-PAGE). In this report an optimized sample preparation protocol for little amount of human post-mortem and mouse brain tissue is described. This method enables to perform both two-dimensional fluorescence difference gel electrophoresis (2D-DIGE) and mini 2DE immunoblotting. The combination of these approaches allows one to not only find new proteins and/or protein modifications in their expression thanks to its compatibility with mass spectrometry detection, but also a new insight into markers validation. Thus, mini-2DE coupled to western blotting permits to identify and validate post-translational modifications, proteins catabolism and provides a qualitative comparison among different conditions and/or treatments. Herein, we provide a method to study components of protein aggregates found in AD and Lewy body dementia such as the amyloid-beta peptide and the alpha-synuclein. Our method can thus be adapted for the analysis of the proteome and insoluble proteins extract from human brain tissue and mice models too. In parallel, it may provide useful information for the study of molecular and cellular pathways involved in neurodegenerative diseases as well as potential novel biomarkers and therapeutic targets. PMID:24747743

  5. Polypathology and dementia after brain trauma: Does brain injury trigger distinct neurodegenerative diseases, or should they be classified together as traumatic encephalopathy?

    PubMed

    Washington, Patricia M; Villapol, Sonia; Burns, Mark P

    2016-01-01

    Neuropathological studies of human traumatic brain injury (TBI) cases have described amyloid plaques acutely after a single severe TBI, and tau pathology after repeat mild TBI (mTBI). This has helped drive the hypothesis that a single moderate to severe TBI increases the risk of developing late-onset Alzheimer's disease (AD), while repeat mTBI increases the risk of developing chronic traumatic encephalopathy (CTE). In this review we critically assess this position-examining epidemiological and case control human studies, neuropathological evidence, and preclinical data. Epidemiological studies emphasize that TBI is associated with the increased risk of developing multiple types of dementia, not just AD-type dementia, and that TBI can also trigger other neurodegenerative conditions such as Parkinson's disease. Further, human post-mortem studies on both single TBI and repeat mTBI can show combinations of amyloid, tau, TDP-43, and Lewy body pathology indicating that the neuropathology of TBI is best described as a 'polypathology'. Preclinical studies confirm that multiple proteins associated with the development of neurodegenerative disease accumulate in the brain after TBI. The chronic sequelae of both single TBI and repeat mTBI share common neuropathological features and clinical symptoms of classically defined neurodegenerative disorders. However, while the spectrum of chronic cognitive and neurobehavioral disorders that occur following repeat mTBI is viewed as the symptoms of CTE, the spectrum of chronic cognitive and neurobehavioral symptoms that occur after a single TBI is considered to represent distinct neurodegenerative diseases such as AD. These data support the suggestion that the multiple manifestations of TBI-induced neurodegenerative disorders be classified together as traumatic encephalopathy or trauma-induced neurodegeneration, regardless of the nature or frequency of the precipitating TBI. PMID:26091850

  6. Influence of porcine circovirus type 2 vaccination on the probability and severity of pneumonia detected postmortem

    PubMed Central

    Raith, J.; Kuchling, S.; Schleicher, C.; Schobesberger, H.; Köfer, J.

    2015-01-01

    To evaluate the influence of porcine circovirus type 2 vaccination (PCV-2) on the probability and severity of pneumonia, postmortem findings of 247,505 pigs slaughtered between 2008 and 2011 were analysed by applying a cumulative link mixed model. Three major effects could be observed: (1) PCV-2 vaccination significantly (P<0.01) reduced the odds (coefficient: −0.05) of postmortem findings of mild, moderate and severe pneumonia for vaccinated pigs. (2) Pigs from fattening farms were less likely (coefficient: −0.44; P<0.05) to exhibit signs of pneumonia at slaughter than pigs from farrow-to-finish farms. (3) When vaccinated, the odds of detecting postmortem signs showed an even more pronounced reduction (coefficient: −0.19; P<0.001) for pigs from fattening farms. Combining PCV-2 vaccination, farm type and interaction effects between these two factors, a pig vaccinated against PCV-2 from a fattening farm had only half the chance (OR 0.51) of pneumonia being detected at postmortem than a non-vaccinated pig from a farrow-to-finish farm. The study demonstrates the benefit of a vaccination programme against PCV-2 as an important tool to reduce the risk of postmortem pneumonia findings and the severity of pneumonia in pigs at slaughter. PMID:25413158

  7. Postmortem diffusion of n-butane and i-butane used for anticontagious plugging spray.

    PubMed

    Okuda, Katsuhiro; Maseda, Chikatoshi; Asari, Masaru; Isozaki, Shotaro; Kiya, Hiroshi; Yajima, Daisuke; Shiono, Hiroshi; Shimizu, Keiko

    2016-03-01

    Blood and tissue samples from a forensic autopsy of a man in his late 60s, who developed dementia and died of multiple head traumas due to a fall from a moving vehicle, contained certain amounts of n-butane and i-butane. The concentration of n-butane was in the range of 0.48-70.5 μL/g, which would be considered as toxic or lethal levels. We had to distinguish whether the cause of his unexplained behavior was due to his pre-existing condition (dementia), or from a confused state induced by butane abuse. No traces of butane use were found at the scene. Police investigation revealed that a propellant used in an anticontagious plugging spray had been administered to him during a postmortem treatment in the emergency hospital. In order to prove the postmortem butane diffusion had resulted from the spray administration and to estimate the diffused concentration, experimental simulation was conducted by using rats. As a result of postmortem treatment with the spray, n-butane at concentrations of 0.54-15.5 μL/mL or g were found in the rat blood and tissues. In this case, we provided further evidence that the postmortem butane diffusion, caused by using the anticontagious plugging spray containing butane gas as a propellant administered to a cadaver during a postmortem procedure prior to forensic autopsy, should be distinguished from cases of actual butane poisoning. PMID:26318540

  8. Postmortem serum endotoxin level in relation to the causes of death.

    PubMed

    Zhu, Bao-Li; Ishikawa, Takaki; Michiue, Tomomi; Quan, Li; Maeda, Hitoshi

    2005-03-01

    Serum endotoxin is a clinical marker of sepsis. However, it is vulnerable to bacterial contamination, and the postmortem stability has not been established. In the present study, to evaluate the forensic pathological significance of postmortem endotoxemia in relation to the causes of death, we investigated a series of 111 autopsy cases (postmortem interval<48 h), in part, using bacteriological investigations. Systemic endotoxemia involving both the cardiac and peripheral blood was observed in some specific causes of death, including pneumonia (n=1/3), peritonitis (n=2/5), delayed traumatic death with severe secondary infection (n=7/33), drownings (freshwater, n=3/9; saltwater, n=3/16), fire deaths (n=3/16), and also in protracted deaths under critical medical care (n=2). Most cases of fatal blunt injury (n=4/5) showed sporadic endotoxemia in cardiac or peripheral blood, whereas there was no elevation of serum endotoxin in acute hemorrhagic death from sharp instrument injury (n=6). The bacteriological investigation showed some characteristic profiles in infections and drownings. These observations suggested that, although endotoxin is a vulnerable serum marker to ante and postmortem interference, systemic postmortem endotoxemia involving peripheral blood may be a possible indicator of antemortem bacteremia related to some specific causes of death accompanied by advanced infection or pulmonary alveolar damage in the dying process especially due to drownings and fires. PMID:15708333

  9. Afamin is synthesized by cerebrovascular endothelial cells and mediates α-tocopherol transport across an in vitro model of the blood–brain barrier

    PubMed Central

    Kratzer, Ingrid; Bernhart, Eva; Wintersperger, Andrea; Hammer, Astrid; Waltl, Sabine; Malle, Ernst; Sperk, Günther; Wietzorrek, Georg; Dieplinger, Hans; Sattler, Wolfgang

    2011-01-01

    α-Tocopherol (αTocH), a member of the vitamin E family, is essential for normal neurological function. Despite the importance of αTocH transport into the CNS, transfer mechanisms across the blood–brain barrier (BBB) are not entirely clear. We here investigate whether afamin, a known αTocH-binding protein, contributes to αTocH transport across an in vitro model of the BBB consisting of primary porcine brain capillary endothelial cells (BCEC) and basolaterally cultured astrocytoma cells. Exogenously added afamin had no adverse effects on BCEC viability or barrier function and was transported across BCEC Transwell cultures. Furthermore, αTocH transport across polarized BCEC cultures to astrocytoma cells is facilitated by afamin, though to a lesser extent than by high-density lipoprotein-mediated transport, an essential and in vivo operating αTocH import pathway at the cerebrovasculature. We also demonstrate that porcine BCEC endogenously synthesize afamin. In line with these in vitro findings, afamin was detected by immunohistochemistry in porcine, human postmortem, and mouse brain, where prominent staining was observed almost exclusively in the cerebrovasculature. The demonstration of afamin mRNA expression in isolated brain capillaries suggests that afamin might be a new family member of binding/transport proteins contributing to αTocH homeostasis at the BBB in vivo. PMID:19046407

  10. AdS3: the NHEK generation

    NASA Astrophysics Data System (ADS)

    Bena, Iosif; Heurtier, Lucien; Puhm, Andrea

    2016-05-01

    It was argued in [1] that the five-dimensional near-horizon extremal Kerr (NHEK) geometry can be embedded in String Theory as the infrared region of an infinite family of non-supersymmetric geometries that have D1, D5, momentum and KK monopole charges. We show that there exists a method to embed these geometries into asymptotically- {AdS}_3× {S}^3/{{Z}}_N solutions, and hence to obtain infinite families of flows whose infrared is NHEK. This indicates that the CFT dual to the NHEK geometry is the IR fixed point of a Renormalization Group flow from a known local UV CFT and opens the door to its explicit construction.

  11. Shadows, currents, and AdS fields

    SciTech Connect

    Metsaev, R. R.

    2008-11-15

    Conformal totally symmetric arbitrary spin currents and shadow fields in flat space-time of dimension greater than or equal to four are studied. A gauge invariant formulation for such currents and shadow fields is developed. Gauge symmetries are realized by involving the Stueckelberg fields. A realization of global conformal boost symmetries is obtained. Gauge invariant differential constraints for currents and shadow fields are obtained. AdS/CFT correspondence for currents and shadow fields and the respective normalizable and non-normalizable solutions of massless totally symmetric arbitrary spin AdS fields are studied. The bulk fields are considered in a modified de Donder gauge that leads to decoupled equations of motion. We demonstrate that leftover on shell gauge symmetries of bulk fields correspond to gauge symmetries of boundary currents and shadow fields, while the modified de Donder gauge conditions for bulk fields correspond to differential constraints for boundary conformal currents and shadow fields. Breaking conformal symmetries, we find interrelations between the gauge invariant formulation of the currents and shadow fields, and the gauge invariant formulation of massive fields.

  12. Usefulness and limitations of postmortem computed tomography in forensic analysis of gunshot injuries: Three case reports.

    PubMed

    Usui, Akihito; Kawasumi, Yusuke; Hosokai, Yoshiyuki; Kozakai, Masataka; Saito, Haruo; Funayama, Masato

    2016-01-01

    Gunshot injury has always been an important field of investigation in postmortem forensic radiology. The localization and retrieval of the bullet and of potentially important fragments are vital to these cases. Using postmortem multidetector-row computed tomography (MDCT) prior to forensic autopsy, we sought to illustrate the importance of this modality in the noninvasive characterization of gunshot wounds. We obtained and analyzed MDCT images in three cases of gunshot wounds (accidental close-range shotgun shooting, suicidal contact gunshot to the head and accidental long-range buckshot shooting). We discuss the value of postmortem MDCT findings in gunshot wound cases by comparing with forensic autopsy findings in Japan, a developing country with miserably low autopsy rate. PMID:26832386

  13. Differences between postmortem computed tomography and conventional autopsy in a stabbing murder case

    PubMed Central

    Zerbini, Talita; da Silva, Luiz Fernando Ferraz; Ferro, Antonio Carlos Gonçalves; Kay, Fernando Uliana; Junior, Edson Amaro; Pasqualucci, Carlos Augusto Gonçalves; do Nascimento Saldiva, Paulo Hilario

    2014-01-01

    OBJECTIVE: The aim of the present work is to analyze the differences and similarities between the elements of a conventional autopsy and images obtained from postmortem computed tomography in a case of a homicide stab wound. METHOD: Comparison between the findings of different methods: autopsy and postmortem computed tomography. RESULTS: In some aspects, autopsy is still superior to imaging, especially in relation to external examination and the description of lesion vitality. However, the findings of gas embolism, pneumothorax and pulmonary emphysema and the relationship between the internal path of the instrument of aggression and the entry wound are better demonstrated by postmortem computed tomography. CONCLUSIONS: Although multislice computed tomography has greater accuracy than autopsy, we believe that the conventional autopsy method is fundamental for providing evidence in criminal investigations. PMID:25518020

  14. Evaluation of Virulence Factors and Antifungal Susceptibility in Yeast Isolates from Postmortem Specimens.

    PubMed

    Yagmur, Gulhan; Sav, Hafize; Ziyade, Nihan; Elgormus, Neval; Sen, Sumeyye; Akkoyun Bilgi, Esma; Atan, Yusuf; Buyuk, Yalcin; Kiraz, Nuri

    2016-07-01

    Invasive fungal infections are a leading cause of morbidity and mortality in immunocompromised patients, especially in cases requiring a prolonged stay in the intensive care unit. A total of 99 yeast strains were isolated from 42 postmortem cases. In this study, virulence factors and antifungal susceptibility of these species were evaluated. The isolates were identified as Candida albicans (54), C. tropicalis (15), C. glabrata (12), C. parapsilosis (6), C. lipolytica (3), C. utilis (3), C. krusei (2), C. kefyr (1), and Cryptococcus neoformans (3). The most commonly isolated species was C. albicans, and no resistant species were determined. Despite the equal number of specimens, no secretion of significant virulence factors was associated with the postmortem specimen in the Candida species. Postmortem fungal investigations in forensic autopsies are useful in explaining cause of death in such cases, also may lead to protocols for the treatment of fungal infections and contribute to fungal pathogenesis and epidemiological data. PMID:27364280

  15. Postmortem redistribution of the heroin metabolites morphine and morphine-3-glucuronide in rabbits over 24 h.

    PubMed

    Maskell, Peter D; Albeishy, Mohammed; De Paoli, Giorgia; Wilson, Nathan E; Seetohul, L Nitin

    2016-03-01

    The interpretation of postmortem drug levels is complicated by changes in drug blood levels in the postmortem period, a phenomena known as postmortem drug redistribution. We investigated the postmortem redistribution of the heroin metabolites morphine and morphine-3-glucuronide in a rabbit model. Heroin (1 mg/kg) was injected into anesthetised rabbit; after 1 h, an auricular vein blood sample was taken and the rabbit was euthanised. Following death rabbits were placed in a supine position at room temperature and divided into three groups namely (1) immediate autopsy, (2) autopsy after 30 minutes and (3) autopsy 24 h after death. Various samples which included femoral blood, cardiac blood, lung, liver, kidney, vitreous humour, subcutaneous and abdominal fat, liver, bone marrow and skeletal muscle were taken. The samples were analysed with a validated LC-MS/MS method. It was observed that within minutes there was a significant increase in free morphine postmortem femoral blood concentration compared to the antemortem sample (0.01 ± 0.01 to 0.05 ± 0.02 mg/L).Various other changes in free morphine and metabolite concentrations were observed during the course of the experiment in various tissues. Principal component analysis was used to investigate possible correlations between free morphine in the various samples. Some correlations were observed but gave poor predictions (>20 % error) when back calculating. The results suggest that rabbits are a good model for further studies of postmortem redistribution but that further study and understanding of the phenomena is required before accurate predictions of the blood concentration at the time of death are possible. PMID:25863436

  16. Effects of probiotics feeding on meat quality of chicken breast during postmortem storage.

    PubMed

    Kim, H W; Yan, F F; Hu, J Y; Cheng, H W; Kim, Y H B

    2016-06-01

    This study evaluated the effects of dietary probiotic supplement and postmortem storage on meat quality of chicken breast during retail display. A total of 35 birds were randomly obtained from 3 feeding groups (control without probiotic supplement, 250 ppm Sporulin, and 500 ppm PoultryStar). The probiotic supplement had no influence on feed conversion ratio and body weight gain, as well as body weight at 29 and 44 d (P > 0.05). After slaughter, each side of the breast muscles (M. Pectoralis major) was assigned to either one d or 5 d of postmortem storage. Probiotic supplement had no influence on the rate of pH decline of chicken breast muscles during the initial 6 h postmortem (P > 0.05). No interactions between probiotic supplement and postmortem storage on meat quality were found (P > 0.05). Postmortem storage decreased drip loss from 25.30 to 18.05% (P < 0.05). Probiotics-fed chicken groups, particularly PoultryStar treatment, had a higher myofibrillar fragmentation index than the control group (P < 0.05). However, shear force values were not affected by the probiotic treatments. Decreases in color and lipid stabilities of breast muscles were found during display (P < 0.05), but were not affected by the probiotic supplement (P > 0.05). Our result suggests that probiotic supplement had no adverse impacts on proteolysis and oxidative changes during 5 d postmortem display storage. PMID:26944974

  17. Postmortem drug concentration intervals for the non-intoxicated state - A review.

    PubMed

    Linnet, Kristian

    2012-07-01

    In postmortem toxicology, it is important to know what the usual drug level is in blood under ordinary therapy to make correct interpretations with regard to the possible occurrence of poisoning. A commonly used source is The International Association of Forensic Toxicologists (TIAFT) list of drug concentrations providing therapeutic drug levels, usually measured in serum. In this article, published postmortem-derived blood drug reference concentration intervals were related to therapeutic serum levels of drugs from the TIAFT list to assess agreement or discrepancies with focus on the importance of postmortem redistribution. The ratio between the upper limits was evaluated. This ratio ranged from 0.13 to 11.3 for 57 compounds with a median value of 1.5. For about a third of the compounds the ratio exceeded three. There was a tendency that for highly water-soluble drugs with a low propensity for redistribution, the ratio was generally low. For example, for pentobarbital, carisoprodol, meprobamate, carbamazepine, phenazone and theophylline, the ratio ranged from 0.14 to 1.1 with a median of 0.4. For the 15 antidepressants considered, on the other hand, the ratio was relatively high, ranging from 0.6 to 4.7 (median 2.4). For antipsychotics, the ratio ranged from 0.2 to 11.3 with a median of 1.4. In conclusion, there were generally wide discrepancies between serum-based intervals as presented in the TIAFT list and published postmortem blood-based drug reference intervals. More focus on postmortem-derived intervals is encouraged, so that those that have been estimated are cited in reference publications and so that further intervals are estimated. Ultimately, a reliable database of postmortem blood-based drug reference intervals for use by the forensic community is desirable. PMID:22687764

  18. Postmortem sperm retrieval in context of developing countries of Indian subcontinent

    PubMed Central

    Sikary, Asit Kumar; Murty, O. P.; Bardale, Rajesh V.

    2016-01-01

    There was a request for postmortem sperm retrieval (PMSR) from the wife of a deceased, but we had to decline. We have no guideline in place for the procedure in such cases. When we explored the international scenario on the issue of PMSR, we found that most of the developed countries have their guidelines about it, whether to allow or not to. There is not guideline available in developing countries, as such, for the procedure and various medical, legal, and social issues related thereto. In this article, we have explored the status of postmortem retrieval and feasibility of the procedure in developing countries of Indian subcontinent. PMID:27382231

  19. Monitoring of Chicken RNA Integrity as a Function of Prolonged Postmortem Duration.

    PubMed

    Malila, Yuwares; Srimarut, Yanee; U-Chupaj, Juthawut; Strasburg, Gale; Visessanguan, Wonnop

    2015-11-01

    Gene expression profiling has offered new insights into postmortem molecular changes associated with meat quality. To acquire reliable transcript quantification, high quality RNA is required. The objective of this study was to analyze integrity of RNA isolated from chicken skeletal muscle (pectoralis major) and its capability of serving as the template in quantitative real-time polymerase chain reaction (qPCR) as a function of postmortem intervals representing the end-points of evisceration, carcass chilling and aging stages in chicken abattoirs. Chicken breast muscle was dissected from the carcasses (n = 6) immediately after evisceration, and one-third of each sample was instantly snap-frozen and labeled as 20 min postmortem. The remaining muscle was stored on ice until the next rounds of sample collection (1.5 h and 6 h postmortem). The delayed postmortem duration did not significantly affect A260/A280 and A260/A230 (p≥0.05), suggesting no altered purity of total RNA. Apart from a slight decrease in the 28s:18s ribosomal RNA ratio in 1.5 h samples (p<0.05), the value was not statistically different between 20 min and 6 h samples (p≥0.05), indicating intact total RNA up to 6 h. Abundance of reference genes encoding beta-actin (ACTB), glyceraldehyde 3-phosphate dehydrogenase (GAPDH), hypoxanthine-guanine phosphoribosyltransferase (HPRT), peptidylprolylisomerase A (PPIA) and TATA box-binding protein (TBP) as well as meat-quality associated genes (insulin-like growth factor 1 (IGF1), pyruvate dehydrogenase kinase isozyme 4 (PDK4), and peroxisome proliferator-activated receptor delta (PPARD) were investigated using qPCR. Transcript abundances of ACTB, GAPDH, HPRT, and PPIA were significantly different among all postmortem time points (p<0.05). Transcript levels of PDK4 and PPARD were significantly reduced in the 6 h samples (p<0.05). The findings suggest an adverse effect of a prolonged postmortem duration on reliability of transcript quantification in chicken

  20. Characterisation of the metabolome of ocular tissues and post-mortem changes in the rat retina.

    PubMed

    Tan, Shi Z; Mullard, Graham; Hollywood, Katherine A; Dunn, Warwick B; Bishop, Paul N

    2016-08-01

    Time-dependent post-mortem biochemical changes have been demonstrated in donor cornea and vitreous, but there have been no published studies to date that objectively measure post-mortem changes in the retinal metabolome over time. The aim of the study was firstly, to investigate post-mortem, time-dependent changes in the rat retinal metabolome and secondly, to compare the metabolite composition of healthy rat ocular tissues. To study post-mortem changes in the rat retinal metabolome, globes were enucleated and stored at 4 °C and sampled at 0, 2, 4, 8, 24 and 48 h post-mortem. To study the metabolite composition of rat ocular tissues, eyes were dissected immediately after culling to isolate the cornea, lens, vitreous and retina, prior to storing at -80 °C. Tissue extracts were subjected to Gas Chromatograph Mass Spectrometry (GC-MS) and Ultra High Performance Liquid Chromatography Mass Spectrometry (UHPLC-MS). Generally, the metabolic composition of the retina was stable for 8 h post-mortem when eyes were stored at 4 °C, but showed increasing changes thereafter. However, some more rapid changes were observed such as increases in TCA cycle metabolites after 2 h post-mortem, whereas some metabolites such as fatty acids only showed decreases in concentration from 24 h. A total of 42 metabolites were identified across the ocular tissues by GC-MS (MSI level 1) and 2782 metabolites were annotated by UHPLC-MS (MSI level 2) according to MSI reporting standards. Many of the metabolites detected were common to all of the tissues but some metabolites showed partitioning between different ocular structures with 655, 297, 93 and 13 metabolites being uniquely detected in the retina, lens, cornea and vitreous respectively. Only a small percentage (1.6%) of metabolites found in the vitreous were only detected in the retina and not other tissues. In conclusion, mass spectrometry-based techniques have been used for the first time to compare the metabolic composition of

  1. Monitoring of Chicken RNA Integrity as a Function of Prolonged Postmortem Duration

    PubMed Central

    Malila, Yuwares; Srimarut, Yanee; U-chupaj, Juthawut; Strasburg, Gale; Visessanguan, Wonnop

    2015-01-01

    Gene expression profiling has offered new insights into postmortem molecular changes associated with meat quality. To acquire reliable transcript quantification, high quality RNA is required. The objective of this study was to analyze integrity of RNA isolated from chicken skeletal muscle (pectoralis major) and its capability of serving as the template in quantitative real-time polymerase chain reaction (qPCR) as a function of postmortem intervals representing the end-points of evisceration, carcass chilling and aging stages in chicken abattoirs. Chicken breast muscle was dissected from the carcasses (n = 6) immediately after evisceration, and one-third of each sample was instantly snap-frozen and labeled as 20 min postmortem. The remaining muscle was stored on ice until the next rounds of sample collection (1.5 h and 6 h postmortem). The delayed postmortem duration did not significantly affect A260/A280 and A260/A230 (p≥0.05), suggesting no altered purity of total RNA. Apart from a slight decrease in the 28s:18s ribosomal RNA ratio in 1.5 h samples (p<0.05), the value was not statistically different between 20 min and 6 h samples (p≥0.05), indicating intact total RNA up to 6 h. Abundance of reference genes encoding beta-actin (ACTB), glyceraldehyde 3-phosphate dehydrogenase (GAPDH), hypoxanthine-guanine phosphoribosyltransferase (HPRT), peptidylprolylisomerase A (PPIA) and TATA box-binding protein (TBP) as well as meat-quality associated genes (insulin-like growth factor 1 (IGF1), pyruvate dehydrogenase kinase isozyme 4 (PDK4), and peroxisome proliferator-activated receptor delta (PPARD) were investigated using qPCR. Transcript abundances of ACTB, GAPDH, HPRT, and PPIA were significantly different among all postmortem time points (p<0.05). Transcript levels of PDK4 and PPARD were significantly reduced in the 6 h samples (p<0.05). The findings suggest an adverse effect of a prolonged postmortem duration on reliability of transcript quantification in chicken

  2. Postmortem sperm retrieval in context of developing countries of Indian subcontinent.

    PubMed

    Sikary, Asit Kumar; Murty, O P; Bardale, Rajesh V

    2016-01-01

    There was a request for postmortem sperm retrieval (PMSR) from the wife of a deceased, but we had to decline. We have no guideline in place for the procedure in such cases. When we explored the international scenario on the issue of PMSR, we found that most of the developed countries have their guidelines about it, whether to allow or not to. There is not guideline available in developing countries, as such, for the procedure and various medical, legal, and social issues related thereto. In this article, we have explored the status of postmortem retrieval and feasibility of the procedure in developing countries of Indian subcontinent. PMID:27382231

  3. Investigation of Post-mortem Tissue Effects Using Long-time Decorrelation Ultrasound

    NASA Astrophysics Data System (ADS)

    Csány, Gergely; Balogh, Lajos; Gyöngy, Miklós

    Decorrelation ultrasound is being increasingly used to investigate long-term biological phenomena. In the current work, ultrasound image sequences of mice who did not survive anesthesia (in a separate investigation) were analyzed and post-mortem tissue effects were observed via decorrelation calculation. A method was developed to obtain a quantitative parameter characterizing the rate of decorrelation. The results show that ultrasound decorrelation imaging is an effective method of observing post-mortem tissue effects and point to further studies elucidating the mechanism behind these effects.

  4. Effect of pH and postmortem aging on protein extraction from broiler breast muscle.

    PubMed

    Eady, M; Samuel, D; Bowker, B

    2014-07-01

    This study determined the effects of extraction buffer pH and postmortem aging on the extraction of salt-soluble and water-soluble proteins from broiler pectoralis muscle. Deboned broiler breast fillets were collected at 4 h postmortem, packaged, and then stored at 4°C until 1, 5, or 8 d postmortem. After the designated aging period, salt-soluble and water-soluble protein extractions were performed using buffers at 7 different pH levels (pH 5.4, 6.4, 6.9, 7.2, 7.5, 8.0, 9.0). Protein concentrations of the extracts were measured and SDS-PAGE analysis was performed. Salt-soluble protein concentration increased (P < 0.0001) as buffer pH increased from pH 5.4 to 6.9 and then remained unchanged from pH 6.9 to 9.0. Water-soluble protein concentration increased (P < 0.0001) as buffer pH increased from pH 5.4 to 7.2 and then remained unchanged from pH 7.2 to 9.0. There was not a significant extraction buffer pH by aging treatment interaction for the total protein concentration of either the salt-soluble or water-soluble protein extracts. The protein concentrations of salt-soluble extracts were similar at both 1 and 8 d postmortem but lower (P < 0.0001) at 5 d postmortem. The protein concentrations of water-soluble extracts were similar at both 1 and 5 d postmortem, but higher (P < 0.0001) at 8 d. Both extraction buffer pH and postmortem aging influenced the SDS-PAGE protein profiles of salt-soluble and water-soluble protein extracts from breast muscles. Data demonstrate that postmortem aging and extraction buffer pH influence both the total amount and the composition of the myofibrillar and sarcoplasmic proteins that can be extracted from broiler breast fillets. PMID:24812239

  5. Distribution of ∆(9)-Tetrahydrocannabinol and 11-Nor-9-Carboxy-∆(9)-Tetrahydrocannabinol Acid in Postmortem Biological Fluids and Tissues From Pilots Fatally Injured in Aviation Accidents.

    PubMed

    Kemp, Philip M; Cardona, Patrick S; Chaturvedi, Arvind K; Soper, John W

    2015-07-01

    Little is known of the postmortem distribution of ∆(9)-tetrahydrocannabinol (THC) and its major metabolite, 11-nor-9-carboxy-∆(9)-tetrahydrocannabinol (THCCOOH). Data from 55 pilots involved in fatal aviation accidents are presented in this study. Gas chromatography/mass spectrometry analysis obtained mean THC concentrations in blood from multiple sites, liver, lung, and kidney of 15.6 ng/mL, 92.4 ng/g, 766.0 ng/g, 44.1 ng/g and mean THCCOOH concentrations of 35.9 ng/mL, 322.4 ng/g, 42.6 ng/g, 138.5 ng/g, respectively. Heart THC concentrations (two cases) were 184.4 and 759.3 ng/g, and corresponding THCCOOH measured 11.0 and 95.9 ng/g, respectively. Muscle concentrations for THC (two cases) were 16.6 and 2.5 ng/g; corresponding THCCOOH, "confirmed positive" and 1.4 ng/g. The only brain tested in this study showed no THC detected and 2.9 ng/g THCCOOH, low concentrations that correlated with low values in other specimens from this case. This research emphasizes the need for postmortem cannabinoid testing and demonstrates the usefulness of a number of tissues, most notably lung, for these analyses. PMID:25800046

  6. Explanations of AD in ethnic minority participants undergoing cognitive screening.

    PubMed

    Tappen, Ruth M; Gibson, Sandra E; Williams, Christine L

    2011-06-01

    The purpose of this study was to describe and compare explanations of Alzheimer's disease (AD) of African American, Afro-Caribbean, and European American older adults undergoing cognitive screening. Participants were asked a series of open-ended questions regarding what they knew about AD and if they were experiencing memory problems. Responses were coded and quantized for analysis. Forty percent reported experiencing memory problems. Afro-Caribbeans made significantly more incorrect statements about AD and were less likely to identify memory loss as a symptom. Half the participants said they would seek their physician's advice if the screening was positive; none mentioned a memory disorder center. Misconceptions about AD included the effect of aluminum, brain collapse, relaxed brain, shaking, tremors, and physical illness. More Afro-Caribbeans, all of whom were first generation, had misconceptions about AD. Campaigns to educate the public about AD need to provide culturally sensitive and appropriate information to ethnic minority populations. PMID:21697141

  7. Brain Science, Brain Fiction.

    ERIC Educational Resources Information Center

    Bruer, John T.

    1998-01-01

    Three big ideas from brain science have arisen during the past 20 to 30 years: neural connections form rapidly early in life; critical periods occur in development; and enriched environments profoundly affect brain development during the early years. Current brain research has little to offer educational practice or policy. (10 references) (MLH)

  8. ADS pilot program Plan

    NASA Technical Reports Server (NTRS)

    Clauson, J.; Heuser, J.

    1981-01-01

    The Applications Data Service (ADS) is a system based on an electronic data communications network which will permit scientists to share the data stored in data bases at universities and at government and private installations. It is designed to allow users to readily locate and access high quality, timely data from multiple sources. The ADS Pilot program objectives and the current plans for accomplishing those objectives are described.

  9. Decreased NAA in Gray Matter is Correlated with Decreased Availability of Acetate in White Matter in Postmortem Multiple Sclerosis Cortex

    PubMed Central

    Li, S.; Clements, R.; Sulak, M.; Gregory, R.; Freeman, E.; McDonough, J.

    2013-01-01

    Multiple sclerosis (MS) is an inflammatory neurodegenerative disease of the central nervous system (CNS) which leads to progressive neurological disability. Our previous studies have demonstrated mitochondrial involvement in MS cortical pathology and others have documented decreased levels of the neuronal mitochondrial metabolite N-acetyl aspartate (NAA) in the MS brain. While NAA is synthesized in neurons, it is broken down in oligodendrocytes into aspartate and acetate. The resulting acetate is incorporated into myelin lipids, linking neuronal mitochondrial function to oligodendrocyte-mediated elaboration of myelin lipids in the CNS. In the present study we show that treating human SH-SY5Y neuroblastoma cells with the electron transport chain inhibitor antimycin A decreased levels of NAA as measured by HPLC. To better understand the significance of the relationship between mitochondrial function and levels of NAA and its breakdown product acetate on MS pathology we then quantitated the levels of NAA and acetate in MS and control postmortem tissue blocks. Regardless of lesion status, we observed that levels of NAA were decreased 25 and 32 % in gray matter from parietal and motor cortex in MS, respectively, compared to controls. Acetate levels in adjacent white matter mirrored these decreases as evidenced by the 36 and 45 % reduction in acetate obtained from parietal and motor cortices. These data suggest a novel mechanism whereby mitochondrial dysfunction and reduced NAA levels in neurons may result in compromised myelination by oligodendrocytes due to decreased availability of acetate necessary for the synthesis of myelin lipids. PMID:24078261

  10. Brain gene expression patterns differentiate Mild Cognitive Impairment from normal Aged and Alzheimer Disease

    PubMed Central

    Berchtold, Nicole C.; Sabbagh, Marwan N.; Beach, Thomas G.; Kim, Ronald C.; Cribbs, David H.; Cotman, Carl W.

    2014-01-01

    Mild cognitive impairment (MCI) represents a cognitive state intermediate between normal aging and early Alzheimer Disease (AD). To investigate if the molecular signature of MCI parallels the clinical picture, we use microarrays to extensively profile gene expression in 4 cortical brain regions (entorhinal cortex, hippocampus, superior frontal gyrus, post-central gyrus) using post-mortem tissue from cognitively normal aged controls, MCI, and AD cases. Our data reveal that gene expression patterns in MCI are not an extension of aging, and for the most part, are not intermediate between aged controls and AD. Functional enrichment analysis of significant genes revealed prominent upregulation in MCI brains of genes associated with anabolic and biosynthetic pathways (notably transcription, protein biosynthesis, protein trafficking and turnover) as well as mitochondrial energy generation. In addition, many synaptic genes showed altered expression in MCI, predominantly upregulation, including genes for central components of the vesicle fusion machinery at the synapse, synaptic vesicle trafficking, neurotransmitter receptors, and synaptic structure and stabilization. These data suggest that there is a rebalancing of synaptic transmission in the MCI brain. To investigate if synaptic gene expression levels in MCI were related to cognitive function, Pearson’s correlation coefficient between MMSE and region-specific mRNA expression were computed for MCI cases. A number of synaptic genes showed strong significant correlations (r>0.8, p<0.01) most notably in the EC, with fewer in the HC, and very few in neocortical regions. The synaptic genes with highly significant correlations were predominantly related to synaptic transmission and plasticity, and myelin composition. Unexpectedly, we found that gene expression changes that facilitate synaptic excitability and plasticity were overwhelmingly associated with poorer MMSE, and conversely that gene expression changes that inhibit

  11. Postmortem Menkes diagnosis from carrier testing of female relatives.

    PubMed

    Tønnesen, T; Silengo, M; Gerdes, A M; Hansen, J C; Reske-Nielsen, E; Franceschini, P; Horn, N

    1987-12-01

    A boy who died at 6 months of age was noted to have sparse, stubby and light hair, pili torti were observed microscopically, and his skin was dry and redundant. As a suspicion of Menkes disease was first raised after his death, serum copper and ceruloplasmin in serum were not measured. Unfortunately, no fibroblasts were available - only fixed and paraffin-embedded samples of brain, spleen and liver. The copper contents of the brain and the liver were lower than in an age-matched control. Fibroblast cultures from the mother, the maternal grandmother, and a maternal aunt of the index patient were analysed for 64Cu-uptake. All these females showed the uptake values expected for Menkes carriers, thus supporting the clinical suspicion of Menkes disease in the index patient. From the above-mentioned results it was highly likely that the index patient had suffered from Menkes disease. Adequate genetic counseling could thus be offered to the family, and in the next pregnancy a first trimester prenatal diagnosis was performed. PMID:3436089

  12. Postmortem distribution of guaifenesin concentrations reveals a lack of potential for redistribution.

    PubMed

    McIntyre, Iain M; Navarrete, Aylmer; Mena, Othon

    2014-12-01

    Therapeutic (or non-toxic) postmortem guaifenesin blood and liver concentrations have not been previously described. Peripheral blood guaifenesin concentrations were compared to central blood and liver concentrations in eight medical examiner cases. Specimens were initially screened for alcohol and simple volatiles, drugs of abuse, alkaline, and acid/neutral drugs. Guaifenesin, when detected by the acid/neutral drug screen, was subsequently confirmed and quantified by a high performance liquid chromatography procedure. Data suggest that postmortem guaifenesin peripheral blood concentrations may be considered non-toxic to at least 5.4mg/L with liver concentrations to at least 7.0mg/kg. Overall, guaifenesin concentrations ranged from 1.9 to 40mg/L in peripheral blood, 2.2-150mg/L in central blood, and 2.6-36mg/kg in liver. The median guaifenesin central blood to peripheral blood ratio was 1.1 (N=8). Similarly, liver to peripheral blood ratios showed a median value of 0.9L/kg (N=5). Given that a liver to peripheral blood ratio less than 5L/kg is consistent with little to no propensity for postmortem redistribution, these data suggest that guaifenesin is not prone to substantial postmortem redistribution. PMID:25447180

  13. Fatal fentanyl patch misuse in a hospitalized patient with a postmortem increase in fentanyl blood concentration.

    PubMed

    Moore, Philip W; Palmer, Robert B; Donovan, Joseph Ward

    2015-01-01

    Opioid-related mortality happens, even in healthcare settings. We describe serial postmortem fentanyl blood concentrations in a hospital inpatient who fatally abused transdermal fentanyl. This is a single-patient case report. A 42-year-old man with lymphoma was started on transdermal fentanyl therapy while hospitalized for chronic abdominal pain. The patient was last seen awake 1.3 h prior to being found apneic and cyanotic. During the resuscitation attempt, a small square-shaped film was removed from the patient's oropharynx. Femoral blood was collected 0.5 and 2 h postmortem, and the measured fentanyl concentration increased from 1.6 to 14 ng/mL. Study limitations include potential laboratory or collection errors and missing data. (i) Providers must be vigilant for signs of fentanyl patch abuse. (ii) Postmortem blood concentrations are not static postmortem, likely secondary to decreasing pH, increased aqueous solubility, and tissue redistribution, and are therefore unlikely to accurately represent antemortem blood concentrations. PMID:25041753

  14. 9 CFR 355.41 - Antemortem and postmortem inspection for mules.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 9 Animals and Animal Products 2 2010-01-01 2010-01-01 false Antemortem and postmortem inspection for mules. 355.41 Section 355.41 Animals and Animal Products FOOD SAFETY AND INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE AGENCY ORGANIZATION AND TERMINOLOGY; MANDATORY MEAT AND POULTRY PRODUCTS INSPECTION AND VOLUNTARY INSPECTION AND...

  15. Effect of chilling method and post-mortem aging time on broiler breast fillet quality

    Technology Transfer Automated Retrieval System (TEKTRAN)

    A study was conducted to determine the effects of chilling method and post-mortem aging time on broiler breast fillet quality. One hundred-fifty eviscerated broiler carcasses were removed from a commercial processing line prior to chilling and transported to the laboratory. Half of the carcasses we...

  16. Sensory Flavor and Texture Profiles of Cooked Broiler Breast Fillets Deboned at Different Postmortem Times

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Three replicate trials were conducted to compare sensory descriptive profiles of cooked broiler breast fillets (pectoralis major) deboned at 3 postmortem times. In each trial, 30 broiler carcasses (42d old birds) were obtained from a commercial processing plant. Ten carcasses were hot-boned (about 3...

  17. Optoacoustic 3D visualization of changes in physiological properties of mouse tissues from live to postmortem

    NASA Astrophysics Data System (ADS)

    Su, Richard; Ermiliov, Sergey A.; Liopo, Anton V.; Oraevsky, Alexander A.

    2012-02-01

    Using the method of 3D optoacoustic tomography, we studied changes in tissues of the whole body of nude mice as the changes manifested themselves from live to postmortem. The studies provided the necessary baseline for optoacoustic imaging of necrotizing tissue, acute and chronic hypoxia, and reperfusion. They also establish a new optoacoustic model of early postmortem conditions of the whole mouse body. Animals were scanned in a 37°C water bath using a three-dimensional optoacoustic tomography system previously shown to provide high contrast maps of vasculature and organs based on changes in the optical absorbance. The scans were performed right before, 5 minutes after, 2 hours and 1 day after a lethal injection of KCl. The near-infrared laser wavelength of 765 nm was used to evaluate physiological features of postmortem changes. Our data showed that optoacoustic imaging is well suited for visualization of both live and postmortem tissues. The images revealed changes of optical properties in mouse organs and tissues. Specifically, we observed improvements in contrast of the vascular network and organs after the death of the animal. We associated these with reduced optical scattering, loss of motion artifacts, and blood coagulation.

  18. Post-Mortem Corneal Thickness Measurements with a Portable Optical Coherence Tomography System: a Reliability Study

    PubMed Central

    Napoli, Pietro Emanuele; Nioi, Matteo; d’Aloja, Ernesto; Fossarello, Maurizio

    2016-01-01

    The purpose of this study was to determine the repeatability and reproducibility of post-mortem central corneal thickness (CCT) measurements by using a real-time, portable optical coherence tomography (OCT) system on an animal model, and to prospectively evaluate the time-course of post-mortem changes in CCT. Forty-six ocular globes of sheep (Ovis aries) were analyzed with a portable spectral-domain OCT device by two operators at different postmortem intervals (PMIs) as follows: immediately (i.e. within 10 minutes), at the 30th minute, at the 1st, 6th, 12th, 24th and 48th hour, and later (up to the 96th hour). The coefficient of repeatability ranged from 0.3% to 3.5%, and coefficients of reproducibility ranged from 0.2% to 3.7% in the central region of the cornea. The intraclass correlation coefficients were particularly high at different PMIs, thus confirming good measurement reliability with the portable OCT. The average CCT decreased immediately and then increased thereafter, with two peaks at 6 and 24 hours after death. Our results suggest that portable OCT is a reliable tool for monitoring CCT variations after death and may be useful in characterizing corneas before explantation, detecting quantitative variations during post-mortem corneal degeneration or assessing changes in CCT for forensic implications. PMID:27457021

  19. Postmortem interactions of muscle temperature, pH and extension on beef quality.

    PubMed

    Bruce, H L; Ball, R O

    1990-12-01

    The effect of pH, temperature and structural damage of muscle early postmortem on the quality of beef, particularly tenderness, was examined in a randomized complete block design with a 2 x 2 x 2 factorial. Semitendinosus muscles were excised from the right sides of 64 Charolais crossbred steer carcasses, placed in a restraint device in a controlled environment and subjected to high (31 degrees C) or low (20 degrees C) temperature, high (control) or low (electrically stimulated) pH and restraint at excised length or restraint at 125% of excised length for 15 min early postmortem. Temperature, pH, shrink, drip loss, cooking loss, sarcomere length, fragmentation index, shear force, color reflectance and collagen and protein solubilities of the muscles were measured after 7 d of aging at 2 degree C. High-temperature aging increased fragmentation index and color reflectance and decreased protein solubility (P less than .05). Decreasing pH via electrical stimulation increased sarcomere length of the muscles aged at the high temperature only (P less than .05). Extension of muscles prior to aging lowered shear force values of the low-temperature muscles compared with the high-temperature muscles (6.12 vs 7.84 kg, SE .38). Stimulation of the muscles also decreased collagen solubility in the high-temperature, extended muscles. Although postmortem temperature and pH were the factors that influenced meat quality most, early postmortem extension should be considered as a modulating variable of meat tenderness. PMID:2286558

  20. 9 CFR 355.41 - Antemortem and postmortem inspection for mules.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... Animal Food, Mule Meat By-Product § 355.41 Antemortem and postmortem inspection for mules. (a)(1) An... for mules. 355.41 Section 355.41 Animals and Animal Products FOOD SAFETY AND INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE AGENCY ORGANIZATION AND TERMINOLOGY; MANDATORY MEAT AND POULTRY PRODUCTS...

  1. Use of postmortem radiographs for the investigation of underwater and hyperbaric deaths.

    PubMed

    Calder, I M

    1987-03-01

    The use of postmortem radiographs as a useful adjunct in the investigation of hyperbaric and immersion deaths is discussed. This technique enables accurate identification of gas within cavities that otherwise could not be detected at routine autopsy, which may also be artifact. In addition it is possible to define bone lesions that need a histologic diagnosis. PMID:3576844

  2. Sarcomere length dynamics of postmortem ovine Psoas major and Longissimus dorsi muscles.

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Understanding relationships between biological mechanisms of postmortem events in muscle and meat quality is of enormous importance for the meat industry. Because sarcomere length has been previously related to tenderness issues in lambs, we decided to study two contrasting types of muscle with know...

  3. The Design and Development of a Post-Mortem Room Complex

    ERIC Educational Resources Information Center

    Osborne, A. D.

    1977-01-01

    The design of a post-mortem room complex to serve the needs of three separate organizations on the campus of the University of Bristol's Veterinary Field Station is described. Comments are made on disadvantages that have become apparent during eight years of use. (Author/LBH)

  4. Moisture absorption early postmortem predicts ultimate drip loss in fresh pork.

    PubMed

    Kapper, C; Walukonis, C J; Scheffler, T L; Scheffler, J M; Don, C; Morgan, M T; Forrest, J C; Gerrard, D E

    2014-02-01

    Water-holding capacity is the ability of meat to hold moisture and is subject to postmortem metabolism. The objective of this study was to characterize the loss of moisture from muscle postmortem and investigate whether these losses are useful in predicting the ultimate drip loss of fresh pork. Cotton-rayon absorptive-based devices were inserted in the longissimus dorsi muscles of pork carcasses (n = 51) postmortem and removed at various intervals for 24h. Greatest moisture absorption was observed at 105 min post exsanguination. Drip loss varied (0.6-15.3%) across carcasses. Individual absorption at 75 min correlated (r = 0.33) with final drip loss. Correlations improved using individual absorption values at 90 min (r = 0.48) and accumulated absorption values at 150 min (r = 0.41). Results show that significant moisture is lost from muscle tissue early postmortem and suggest that capture of this moisture may be useful in predicting final drip loss of fresh meat. PMID:24225387

  5. Post-Mortem Corneal Thickness Measurements with a Portable Optical Coherence Tomography System: a Reliability Study.

    PubMed

    Napoli, Pietro Emanuele; Nioi, Matteo; d'Aloja, Ernesto; Fossarello, Maurizio

    2016-01-01

    The purpose of this study was to determine the repeatability and reproducibility of post-mortem central corneal thickness (CCT) measurements by using a real-time, portable optical coherence tomography (OCT) system on an animal model, and to prospectively evaluate the time-course of post-mortem changes in CCT. Forty-six ocular globes of sheep (Ovis aries) were analyzed with a portable spectral-domain OCT device by two operators at different postmortem intervals (PMIs) as follows: immediately (i.e. within 10 minutes), at the 30(th) minute, at the 1(st), 6(th), 12(th), 24(th) and 48(th) hour, and later (up to the 96(th) hour). The coefficient of repeatability ranged from 0.3% to 3.5%, and coefficients of reproducibility ranged from 0.2% to 3.7% in the central region of the cornea. The intraclass correlation coefficients were particularly high at different PMIs, thus confirming good measurement reliability with the portable OCT. The average CCT decreased immediately and then increased thereafter, with two peaks at 6 and 24 hours after death. Our results suggest that portable OCT is a reliable tool for monitoring CCT variations after death and may be useful in characterizing corneas before explantation, detecting quantitative variations during post-mortem corneal degeneration or assessing changes in CCT for forensic implications. PMID:27457021

  6. Alterations in the sarcoplasmic protein fraction of beef muscle with postmortem aging and hydrodynamic pressure processing

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Capillary electrophoresis (CE) and reversed-phase high performance liquid chromatography (RP-HPLC) analysis were utilized to detect differences in the sarcoplasmic protein profiles of beef strip loins subjected to aging and hydrodynamic pressure processing (HDP) treatments. At 48 h postmortem, stri...

  7. Effect of Chilling Method and Post-Mortem Aging Time on Broiler Breast Fillet Quality

    Technology Transfer Automated Retrieval System (TEKTRAN)

    A study was conducted to determine the effects of chilling method (dry air or immersion) and post-mortem aging time on broiler breast fillet quality (raw fillet color, raw fillet pH, cook yield and Allo-Kramer shear). One hundred fifty eviscerated broiler carcasses were removed from a commercial p...

  8. Postmortem interval estimation: a novel approach utilizing gas chromatography/mass spectrometry-based biochemical profiling.

    PubMed

    Kaszynski, Richard H; Nishiumi, Shin; Azuma, Takeshi; Yoshida, Masaru; Kondo, Takeshi; Takahashi, Motonori; Asano, Migiwa; Ueno, Yasuhiro

    2016-05-01

    While the molecular mechanisms underlying postmortem change have been exhaustively investigated, the establishment of an objective and reliable means for estimating postmortem interval (PMI) remains an elusive feat. In the present study, we exploit low molecular weight metabolites to estimate postmortem interval in mice. After sacrifice, serum and muscle samples were procured from C57BL/6J mice (n = 52) at seven predetermined postmortem intervals (0, 1, 3, 6, 12, 24, and 48 h). After extraction and isolation, low molecular weight metabolites were measured via gas chromatography/mass spectrometry (GC/MS) and examined via semi-quantification studies. Then, PMI prediction models were generated for each of the 175 and 163 metabolites identified in muscle and serum, respectively, using a non-linear least squares curve fitting program. A PMI estimation panel for muscle and serum was then erected which consisted of 17 (9.7%) and 14 (8.5%) of the best PMI biomarkers identified in muscle and serum profiles demonstrating statistically significant correlations between metabolite quantity and PMI. Using a single-blinded assessment, we carried out validation studies on the PMI estimation panels. Mean ± standard deviation for accuracy of muscle and serum PMI prediction panels was -0.27 ± 2.88 and -0.89 ± 2.31 h, respectively. Ultimately, these studies elucidate the utility of metabolomic profiling in PMI estimation and pave the path toward biochemical profiling studies involving human samples. PMID:26931122

  9. NMR approach for monitoring post-mortem changes in Atlantic salmon fillets stored at 0 and 4°C.

    PubMed

    Shumilina, Elena; Ciampa, Alessandra; Capozzi, Francesco; Rustad, Turid; Dikiy, Alexander

    2015-10-01

    High resolution NMR technique has been used to monitor post-mortem changes in salmon (Salmo salar) fillets upon storage at 4 and 0°C. Thirty-one different fish metabolites influencing freshness and taste properties have been unequivocally assigned by NMR using either available standard compounds or ad hoc acquired 2D (1)H-(1)H TOCSY and (1)H-(13)С HSQC spectra. The monitored fish metabolites include amino acids, dipeptides, sugars, vitamins, biogenic amines, as well as different products of the ATP degradation. The detection and monitoring of biogenic amines by NMR, upon fish storage, is information of interest for consumers, since some of these compounds are toxic. The data from this study shows that NMR spectroscopy also provides the amount of all metabolites necessary for the calculation of the K-index used to express fish freshness. A good correlation was found between the K-index increase and the formation of the undesired biogenic amines. The metabolite concentrations and the K-index found in this work were compared and found coherent with literature data. The performed study reveals the strengths and the suitability of the NMR approach to monitor different biochemical processes occurring during fish storage and qualitatively and quantitatively characterise fish metabolites determining fish quality. PMID:25872421

  10. Brain herniation

    MedlinePlus

    ... herniation; Uncal herniation; Subfalcine herniation; Tonsillar herniation; Herniation - brain ... Brain herniation occurs when something inside the skull produces pressure that moves brain tissues. This is most ...

  11. Nigral dopamine type-1 receptors are reduced in Huntington's disease: A postmortem autoradiographic study using ( sup 3 H)SCH 23390 and correlation with ( sup 3 H)forskolin binding

    SciTech Connect

    Filloux, F.; Wagster, M.V.; Folstein, S.; Price, D.L.; Hedreen, J.C.; Dawson, T.M.; Wamsley, J.K. )

    1990-11-01

    Intrastriatal injection of excitatory amino acids, particularly quinolinic acid, has been proposed as an animal model of Huntington's disease. Such neurotoxic lesions of caudate-putamen result in marked dopamine type-1 (D1) receptor losses in the injected nuclei as well as in the ipsilateral substantia nigra pars reticulata. Postmortem human substantia nigra from Huntington's disease brains and from control brains were examined using in vitro autoradiography. A marked reduction in ({sup 3}H)SCH 23390 binding (labeling D1 receptors) in the substantia nigra of postmortem brains of Huntington's patients was identified, thus paralleling the alterations seen in the animal models. A positive, statistically significant correlation was also encountered between D1 receptor binding (labeled by ({sup 3}H)SCH 23390) and ({sup 3}H)forskolin binding (which identifies adenylate cyclase, a second messenger system linked to D1 receptor activation). The results suggest that in the human--as in lower vertebrates--D1 receptors are located on striatonigral terminals and that D1 receptor loss tends to be paralleled by a reduction in adenylate cyclase. Radioactive agents selective for the D1 receptor may prove useful in future studies of Huntington's disease using positron emission tomography scanning.

  12. Chromatography as Method for Analytical Confirmation of Paracetamol in Postmortem Material Together with Psychoactive Substances

    PubMed Central

    Biscevic-Tokic, Jasmina; Tokic, Nedim; Ibrahimpasic, Elma

    2015-01-01

    Introduction: Paracetamol (Acetaminophen) in addition to aspirin is the most commonly used analgesic and antipyretic medication by millions of patients worldwide. It is an example that paracetamol as medicine that in the world is provided without a doctor’s prescription, can lead to death. Today paracetamol became an integral part of a heroin mixture and is very popular at the street market. The main reason for this is that it can be obtained without a prescription, it is cheap, and by most people well tolerated without side effects. It is probably used for “cutting” the pure heroin, as it says in the jargon, and in that manner from small amount of pure drug is obtained greater amount, which is then sold on the street. The goal is to identify presence of paracetamol, by analytical method of gas chromatography mass spectrometer (GC-MS) in postmortem material together with psychoactive substances. Material and methods: For chemical-toxicological analysis is used biological material collected trough autopsy of 20 deceased people, suspected to have died due to psychoactive substance overdose. All received samples are stored at -20 ° C until analysis at our laboratory. From processed 47 samples that were analyzed in the period from 2014 to 2015, 19 are blood samples, urine 19, 3 samples of stomach contents, and 6 samples of bile content. Deceased were middle-aged, of which only 7 were female. The tested samples were processed according to two methods of extraction. Extraction by XAD-2 resin, and the extraction by the method of salting out with sodium tungstate. Extracts of the samples were then dissolved in chloroform and continued analysis at the analytical instrument. Identification of the paracetamol presence, in the test biological samples is demonstrated by the technique of gas chromatography with mass spectometry (hereinafter referred to as GC-MS). The technique of GC-MS is a selective, sensitive and reliable, and is therefore considered a “gold standard

  13. Innovations Without Added Costs

    ERIC Educational Resources Information Center

    Cereghino, Edward

    1974-01-01

    There is no question that we are in a tight money market, and schools are among the first institutions to feel the squeeze. Therefore, when a plan is offered that provides for innovations without added costs, its something worth noting. (Editor)

  14. What Value "Value Added"?

    ERIC Educational Resources Information Center

    Richards, Andrew

    2015-01-01

    Two quantitative measures of school performance are currently used, the average points score (APS) at Key Stage 2 and value-added (VA), which measures the rate of academic improvement between Key Stage 1 and 2. These figures are used by parents and the Office for Standards in Education to make judgements and comparisons. However, simple…

  15. Beyond Genotype: Serotonin Transporter Epigenetic Modification Predicts Human Brain Function

    PubMed Central

    Nikolova, Yuliya S.; Koenen, Karestan C.; Galea, Sandro; Wang, Chiou-Miin; Seney, Marianne L.; Sibille, Etienne; Williamson, Douglas E.; Hariri, Ahmad R.

    2014-01-01

    We examined epigenetic regulation in regards to behaviorally and clinically relevant human brain function. Specifically, we found that increased promoter methylation of the serotonin transporter gene predicted increased threat-related amygdala reactivity and decreased mRNA expression in postmortem amygdala tissue. These patterns were independent of functional genetic variation in the same region. Furthermore, the association with amygdala reactivity was replicated in a second cohort and was robust to both sampling methods and age. PMID:25086606

  16. A case of fatal sigmoid volvulus visualized on postmortem radiography: The importance of image optimization with multidetector computed tomography.

    PubMed

    Usui, Akihito; Kawasumi, Yusuke; Hosokai, Yoshiyuki; Ishizuka, Yuya; Ikeda, Tomoya; Saito, Haruo; Funayama, Masato

    2016-03-01

    This report describes the case of a man who developed fatal sigmoid volvulus that was identified on postmortem radiography before forensic autopsy. Postmortem radiography is useful for visualizing the body prior to autopsy. We discuss postmortem multidetector computed tomography that was tailored for optimum image quality to allow reconstruction of the fatal findings in multiple axes and in three dimensions, helping to pinpoint the anatomical sites of interest. This involves techniques such as manipulation of the scanning beam pitch and overlapping CT section acquisition. These techniques are best performed by personnel with CT technology training. PMID:26980251

  17. Introducing ADS Labs

    NASA Astrophysics Data System (ADS)

    Accomazzi, Alberto; Henneken, E.; Grant, C. S.; Kurtz, M. J.; Di Milia, G.; Luker, J.; Thompson, D. M.; Bohlen, E.; Murray, S. S.

    2011-05-01

    ADS Labs is a platform that ADS is introducing in order to test and receive feedback from the community on new technologies and prototype services. Currently, ADS Labs features a new interface for abstract searches, faceted filtering of results, visualization of co-authorship networks, article-level recommendations, and a full-text search service. The streamlined abstract search interface provides a simple, one-box search with options for ranking results based on a paper relevancy, freshness, number of citations, and downloads. In addition, it provides advanced rankings based on collaborative filtering techniques. The faceted filtering interface allows users to narrow search results based on a particular property or set of properties ("facets"), allowing users to manage large lists and explore the relationship between them. For any set or sub-set of records, the co-authorship network can be visualized in an interactive way, offering a view of the distribution of contributors and their inter-relationships. This provides an immediate way to detect groups and collaborations involved in a particular research field. For a majority of papers in Astronomy, our new interface will provide a list of related articles of potential interest. The recommendations are based on a number of factors, including text similarity, citations, and co-readership information. The new full-text search interface allows users to find all instances of particular words or phrases in the body of the articles in our full-text archive. This includes all of the scanned literature in ADS as well as a select portion of the current astronomical literature, including ApJ, ApJS, AJ, MNRAS, PASP, A&A, and soon additional content from Springer journals. Fulltext search results include a list of the matching papers as well as a list of "snippets" of text highlighting the context in which the search terms were found. ADS Labs is available at http://adslabs.org

  18. A high fat diet alters metabolic and bioenergetic function in the brain: A magnetic resonance spectroscopy study.

    PubMed

    Raider, Kayla; Ma, Delin; Harris, Janna L; Fuentes, Isabella; Rogers, Robert S; Wheatley, Joshua L; Geiger, Paige C; Yeh, Hung-Wen; Choi, In-Young; Brooks, William M; Stanford, John A

    2016-07-01

    Diet-induced obesity and associated metabolic effects can lead to neurological dysfunction and increase the risk of developing Alzheimer's disease (AD) and Parkinson's disease (PD). Despite these risks, the effects of a high-fat diet on the central nervous system are not well understood. To better understand the mechanisms underlying the effects of high fat consumption on brain regions affected by AD and PD, we used proton magnetic resonance spectroscopy ((1)H-MRS) to measure neurochemicals in the hippocampus and striatum of rats fed a high fat diet vs. normal low fat chow. We detected lower concentrations of total creatine (tCr) and a lower glutamate-to-glutamine ratio in the hippocampus of high fat rats. Additional effects observed in the hippocampus of high fat rats included higher N-acetylaspartylglutamic acid (NAAG), and lower myo-inositol (mIns) and serine (Ser) concentrations. Post-mortem tissue analyses revealed lower phosphorylated AMP-activated protein kinase (pAMPK) in the striatum but not in the hippocampus of high fat rats. Hippocampal pAMPK levels correlated significantly with tCr, aspartate (Asp), phosphoethanolamine (PE), and taurine (Tau), indicating beneficial effects of AMPK activation on brain metabolic and energetic function, membrane turnover, and edema. A negative correlation between pAMPK and glucose (Glc) indicates a detrimental effect of brain Glc on cellular energy response. Overall, these changes indicate alterations in neurotransmission and in metabolic and bioenergetic function in the hippocampus and in the striatum of rats fed a high fat diet. PMID:27125544

  19. Postmortem diffusion of ingested and aspirated paint thinner.

    PubMed

    Fuke, C; Berry, C L; Pounder, D J

    1996-04-23

    Post mortem diffusion of paint thinner (toluene/ethyl acetate/isobutanol 8:1:1 v/v) from gastric residue (25 ml or 100 ml) and airways contamination (25 ml) was assessed in a human cadaver model, with sampling after 24 h at room temperature. Four torso blood samples showed less toluene diffusion after gastric instillation (0.5-3.8 micrograms/ml) than after tracheal instillation (10.5-421 micrograms/ml). Isobutanol diffused more readily than toluene with four torso blood samples 1.8-256 micrograms/ml after gastric instillation and 26-576 micrograms/ml after tracheal instillation. Following 25 ml gastric instillation, toluene concentrations (microgram/ml or microgram/mg) were: pericardial fluid 0.7-4.0; bile 0.5-0.6; urine 0-0.6; brainstem 1.1; lung 0.4-4.4; liver 0-162; spleen 0.6-0.7; kidneys 0.4-0.6; peri-renal fat 0.3-30.3; psoas muscle 0.3-0.8; concentrations of toluene and isobutanol were markedly higher in the left lobe of the liver than the right. Ethyl acetate was mostly undetectable in tissue samples but variably present in five blood samples: 0-21.2 micrograms/ml following 25 ml or 100 ml gastric instillation and 0-198 micrograms/ml following 25 ml tracheal instillation. Ethyl acetate was always detectable in pericardial fluid but not always detectable in gastric contents. We conclude that post mortem diffusion of toluene from gastric residue or airways contamination is unlikely to compromise the analytical validity of femoral venous blood samples, brain, or liver from deep within the right lobe. Analysis of pericardial fluid and gastric contents allows identification of ethyl acetate and isobutanol thus implicating thinner solution. PMID:8635764

  20. Post-mortems in recreational scuba diver deaths: the utility of radiology.

    PubMed

    Wheen, Lyndsae Clair; Williams, Michael Philip

    2009-07-01

    Post-mortem radiology and autopsy findings in a series of six diving-related deaths are presented. The cases had different causes of death but essentially similar radiological findings. We propose that the so-called classical radiological features of cerebral arterial gas embolism more likely represent "off-gassing" (gas coming out of solution into intra-vascular spaces due to pressure changes). As such, we suggest that post-mortem radiology, when accompanying a competent autopsy examination, be limited to the chest, whereby it may be useful in the demonstration of pneumothoraces which might not be demonstrated at autopsy, thereby providing supporting evidence for barotrauma in the context of appropriate clinical and autopsy findings. PMID:19481710

  1. Maggots, mutilations and myth: Patterns of postmortem scavenging of the bovine carcass

    PubMed Central

    Nation, P. Nick; Williams, Elisabeth S.

    1989-01-01

    Based upon what is known about the habits of common carrion eaters in Alberta, we review the patterns of postmortem scavenging of carcasses of cattle. We then compare with these patterns those reported in the lay press and by veterinarians investigating cattle mutilations in Alberta. We conclude that the so-called “mutilation” of cattle in Alberta was due to scavenging of carcasses and further conclude that claims of human involvement in such incidents require, as a first condition, that postmortem scavenging of the carcass be excluded. ImagesFigure 1.Figure 2.Figure 3.Figure 4.Figure 5.Figure 6.Figure 7.Figure 8.Figure 9.Figure 10.Figure 11. PMID:17423422

  2. Viability and infectivity of Ichthyophonus sp. in post-mortem Pacific herring, Clupea pallasii

    USGS Publications Warehouse

    Kocan, Richard M.; Hart, Lucas M.; Lewandowski, Naomi; Hershberger, Paul

    2014-01-01

    Ichthyophonus-infected Pacific herring, Clupea pallasii, were allowed to decompose in ambient seawater then serially sampled for 29 days to evaluate parasite viability and infectivity for Pacific staghorn sculpin, Leptocottus armatus. Ichthyophonus sp. was viable in decomposing herring tissues for at least 29 days post-mortem and could be transmitted via ingestion to sculpin for up to 5 days. The parasite underwent morphologic changes during the first 48 hr following death of the host that were similar to those previously reported, but as host tissue decomposition progressed, several previously un-described forms of the parasite were observed. The significance of long-term survival and continued morphologic transformation in the post-mortem host is unknown, but it could represent a saprozoic phase of the parasite life cycle that has survival value for Ichthyophonus sp.

  3. Relevance of postmortem radiology to the diagnosis of fatal cerebral gas embolism from compressed air diving

    PubMed Central

    Cole, A J; Griffiths, D; Lavender, S; Summers, P; Rich, K

    2006-01-01

    Aims To test the hypothesis that artefact caused by postmortem off‐gassing is at least partly responsible for the presence of gas within the vascular system and tissues of the cadaver following death associated with compressed air diving. Methods Controlled experiment sacrificing sheep after a period of simulated diving in a hyperbaric chamber and carrying out sequential postmortem computed tomography (CT) on the cadavers. Results All the subject sheep developed significant quantities of gas in the vascular system within 24 hours, as demonstrated by CT and necropsy, while the control animals did not. Conclusions The presence of gas in the vascular system of human cadavers following diving associated fatalities is to be expected, and is not necessarily connected with gas embolism following pulmonary barotrauma, as has previously been claimed. PMID:16489175

  4. Postmortem Aging of Beef with a Special Reference to the Dry Aging

    PubMed Central

    Khan, Muhammad I.; Jung, Samooel; Nam, Ki Chang; Jo, Cheorun

    2016-01-01

    Animal muscles are stored for specific period (aging) at refrigerated temperatures, during and after which the living muscles start to convert into meat and thus, attain certain superior properties in the final product. Proteolysis, lipolysis, and oxidation are the major biochemical processes involved during the postmortem aging of meat that affect the tenderness, juiciness, and flavor, as well as sometimes may introduce certain undesirable traits. This review analyzes the role of pre- and post-mortem factors that are important for aging and their effect on the chemical and physical changes in the “dry- and wet-aged meat.” Thus, if the meat processing manufacturers optimize the effects of aging for specific muscles, the palatability, color, and the shelf life of the aged meat products could be significantly enhanced. PMID:27194923

  5. Postmortem Aging of Beef with a Special Reference to the Dry Aging.

    PubMed

    Khan, Muhammad I; Jung, Samooel; Nam, Ki Chang; Jo, Cheorun

    2016-01-01

    Animal muscles are stored for specific period (aging) at refrigerated temperatures, during and after which the living muscles start to convert into meat and thus, attain certain superior properties in the final product. Proteolysis, lipolysis, and oxidation are the major biochemical processes involved during the postmortem aging of meat that affect the tenderness, juiciness, and flavor, as well as sometimes may introduce certain undesirable traits. This review analyzes the role of pre- and post-mortem factors that are important for aging and their effect on the chemical and physical changes in the "dry- and wet-aged meat." Thus, if the meat processing manufacturers optimize the effects of aging for specific muscles, the palatability, color, and the shelf life of the aged meat products could be significantly enhanced. PMID:27194923

  6. Early post-mortem changes and stages of decomposition in exposed cadavers.

    PubMed

    Lee Goff, M

    2009-10-01

    Decomposition of an exposed cadaver is a continuous process, beginning at the moment of death and ending when the body is reduced to a dried skeleton. Traditional estimates of the period of time since death or post-mortem interval have been based on a series of grossly observable changes to the body, including livor mortis, algor mortis, rigor mortis and similar phenomena. These changes will be described briefly and their relative significance discussed. More recently, insects, mites and other arthropods have been increasingly used by law enforcement to provide an estimate of the post-mortem interval. Although the process of decomposition is continuous, it is useful to divide this into a series of five stages: Fresh, Bloated, Decay, Postdecay and Skeletal. Here these stages are characterized by physical parameters and related assemblages of arthropods, to provide a framework for consideration of the decomposition process and acarine relationships to the body. PMID:19554461

  7. Proteome changes on water-holding capacity of yak longissimus lumborum during postmortem aging.

    PubMed

    Zuo, Huixin; Han, Ling; Yu, Qunli; Niu, Kelan; Zhao, Suonan; Shi, Hongmei

    2016-11-01

    To study differentially expressed proteins on water-holding capacity (WHC) during postmortem aging of longissimus lumborum muscle, samples were classified according to drip loss into high and low drip loss groups. Fifty-five proteins were differentially abundant at days 0, 1 and 7 during postmortem aging and identified by MALDI TOF/TOF. The identified proteins can be divided into four main categories: metabolic enzymes, cell structural proteins, stress related proteins and transport proteins. Myosin light chain, heat shock protein 27 and triosephosphate isomerase showed a major difference between the two groups and may have the potential to be biological markers for WHC prediction. Furthermore, bioinformatics analysis revealed that the identified proteins were related to carbon metabolism, glycolysis and biosynthesis of amino acids and pyruvate metabolism. The functions of the identified proteins contribute to a more detailed molecular view of the processes behind WHC and are a valuable resource for future investigations. PMID:27448195

  8. Identifying postmortem microstructural change to skeletal and dental tissues using backscattered electron imaging.

    PubMed

    Bell, Lynne S

    2012-01-01

    A number of papers have been published over a 100 year period describing postmortem microstructural change to bone and teeth in humans and other mammals. Much of the work is descriptive and has used a number of microscopic methods, which introduce changes during preparation, and are limited by the resolving power of that technique. Backscattered electron imaging in a scanning electron microscope (BSE/SEM) has been used successfully applied to on normal skeletal tissues and is an excellent method to document postmortem changes to bone and tooth microstructure. In forensic science, archaeology, and paleontology there is a collective interest in understanding early death history and subsequent treatment and deposition of the body. To this end the main microstructural changes are provided as a means of identification, and practical suggestions to circumvent misinterpretation due to artifacts created by employing the BSE imaging method. PMID:22907409

  9. A microbial clock provides an accurate estimate of the postmortem interval in a mouse model system

    PubMed Central

    Metcalf, Jessica L; Wegener Parfrey, Laura; Gonzalez, Antonio; Lauber, Christian L; Knights, Dan; Ackermann, Gail; Humphrey, Gregory C; Gebert, Matthew J; Van Treuren, Will; Berg-Lyons, Donna; Keepers, Kyle; Guo, Yan; Bullard, James; Fierer, Noah; Carter, David O; Knight, Rob

    2013-01-01

    Establishing the time since death is critical in every death investigation, yet existing techniques are susceptible to a range of errors and biases. For example, forensic entomology is widely used to assess the postmortem interval (PMI), but errors can range from days to months. Microbes may provide a novel method for estimating PMI that avoids many of these limitations. Here we show that postmortem microbial community changes are dramatic, measurable, and repeatable in a mouse model system, allowing PMI to be estimated within approximately 3 days over 48 days. Our results provide a detailed understanding of bacterial and microbial eukaryotic ecology within a decomposing corpse system and suggest that microbial community data can be developed into a forensic tool for estimating PMI. DOI: http://dx.doi.org/10.7554/eLife.01104.001 PMID:24137541

  10. [Postmortem genetic testing in sudden cardiac death due to ion channelopathies].

    PubMed

    Guan, Da-wei; Zhao, Rui

    2010-04-01

    Sudden cardiac death accounts for majority of deaths in human. Evident cardiac lesions that may explain the cause of death can be detected in comprehensive postmortem investigation in most sudden cardiac death. However, no cardiac morphological abnormality is found in a considerable number of cases although the death is highly suspected from cardiac anomaly. With the advances in the modern molecular biology techniques, it has been discovered that many of these sudden deaths are caused by congenital ion channelopathies in myocardial cell, i.e., Brugada syndrome, long QT syndrome, catecholaminergic polymorphic ventricular tachycardia, and short QT syndrome, etc. This article presents the molecular genetics, electrocardiographic abnormalities, clinical manifestations, and mechanisms leading to sudden cardiac death with emphasis on the role of postmortem genetic testing in certification of cause of death. It may provide helpful information in investigating sudden cardiac death due to ion channelopathies in medico-legal practice. PMID:20653139

  11. Postmortem ethanol in the setting of ethanol-containing automotive fuel.

    PubMed

    Garber, Mitchell A; Canfield, Dennis V; Lewis, Russell J; Simmons, Samuel D; Radisch, Deborah L

    2013-03-01

    The pilot of a light aircraft that crashed after a loss of power was found to have ethanol in the vitreous and the blood, but almost none in the urine. The globes of the eyes were intact, and the body was refrigerated after recovery until the autopsy was performed the following morning. The pilot was described as a "nondrinker," and additional specialized toxicology testing results were inconsistent with ethanol ingestion. The pilot's body was extensively exposed to fuel during the prolonged extraction. Investigation determined that the aircraft had been fueled with gasoline that contained 10% ethanol. Although exposure to automotive fuel has not been previously described as a source of ethanol in postmortem specimens, it may represent a source for the ethanol detected during postmortem toxicology testing in this case, and this finding may be relevant to other cases with similar exposure. PMID:22835972

  12. The Relationship Between the Changes in Local Stiffness of Chicken Myofibril and the Tenderness of Muscle During Postmortem Aging

    NASA Astrophysics Data System (ADS)

    Iwasaki, T.; Hasegawa, Y.; Yamamoto, K.; Nakamura, K.

    We have investigated that the relationship between the stiffness of myofibrils and the tenderness of muscle during postmortem aging. The stiffness (elasticity) of A and I bands as well as Z-line of chicken myofibrils during postmortem aging were measured by atomic force microscope. The stiffness of all regions increased till 12 hr of postmortem, then it decreased to 96 hr. This tendency was the same as the changes of shear force value of whole muscle during postmortem aging. The elasticity of the Z-line of chicken myofibrils treated with calcium ions in the presence of protease inhibitor decreased with treating time. This indicates that the nonenzymatic structural changes of myofibrils is one of the causes of meat tenderization.

  13. Postmortem changes in actomyosin dissociation, myofibril fragmentation and endogenous enzyme activities of grass carp (Ctenopharyngodon idellus) muscle.

    PubMed

    Wang, Daoying; Zhang, Muhan; Deng, Shaoying; Xu, Weimin; Liu, Yuan; Geng, Zhiming; Sun, Chong; Bian, Huan; Liu, Fang

    2016-04-15

    The changes of actomyosin, proteolytic activities and myofibril fragmentation during the postmortem aging of grass carp were studied. The study revealed dramatically increased actomyosin dissociation within 6 h of storage postmortem in grass carp, and it was associated with the drop of pH from 6.9 to 6.7, while liberated actin remained almost unchanged after 6 h postmortem. The myofibril fragmentation also increased significantly with the storage time in 6 h, and a highly positive correlation (P<0.01) existed between MFI and cathepsin B, D, H activities. The study indicated both actomyosin dissociation and cathepsin B, D, H played a role in postmortem tenderization and textural changes in grass carp. PMID:26616958

  14. Two Virasoro symmetries in stringy warped AdS3

    NASA Astrophysics Data System (ADS)

    Compère, Geoffrey; Guica, Monica; Rodriguez, Maria J.

    2014-12-01

    We study three-dimensional consistent truncations of type IIB supergravity which admit warped AdS3 solutions. These theories contain subsectors that have no bulk dynamics. We show that the symplectic form for these theories, when restricted to the non-dynamical subsectors, equals the symplectic form for pure Einstein gravity in AdS3. Consequently, for each consistent choice of boundary conditions in AdS3, we can define a consistent phase space in warped AdS3 with identical conserved charges. This way, we easily obtain a Virasoro × Virasoro asymptotic symmetry algebra in warped AdS3; two different types of Virasoro × Kač-Moody symmetries are also consistent alternatives.

  15. Endogenous concentrations of GHB in postmortem blood from deaths unrelated to GHB use.

    PubMed

    Korb, Ann-Sophie; Cooper, Gail

    2014-10-01

    Gamma-hydroxybutyrate (GHB) is an endogenous compound, but its presence in postmortem blood presents a challenge when interpreting elevated levels as GHB is misused as a recreational drug and is also produced postmortem. A total of 387 postmortem cases (273 male and 114 female) submitted to the toxicology laboratory between 2010 and 2012 specifically requested the analysis of the ketoacidosis biomarker, beta-hydroxybutyrate (BHB). No reference to GHB use was identified in any of the case files; however, BHB and GHB are measured simultaneously using deuterated GHB as the internal standard (GHB-d6) within a calibration range of 5-500 mg/L. GHB was not detected or <10 mg/L in 18% of the cases (n = 68), between 10 and 50 mg/L in 73% of the cases (n = 283) and between 51 and 193 mg/L in 9% of the cases (n = 36). The manner of death was classified as accidental (n = 11), alcohol-related (n = 237), drug-related (n = 23), homicide (n = 1), natural (n = 91), suicide (n = 9), medical-related (n = 1) and undetermined (n = 14). Six cases had GHB concentrations in excess of 100 mg/L with advanced decomposition changes noted in five of these cases. Moderate-to-advanced decomposition was also noted in 50% (n = 15) of the cases with GHB concentrations in excess of 50 mg/L but <100 mg/L. Approximately one-third of the blood samples tested contained a preservative and although a higher proportion of these samples had GHB concentrations <10 mg/L or not detected (∼30% preserved versus 11% unpreserved), there were still cases with GHB concentrations >51 mg/L (∼6% preserved versus 11% unpreserved). This study highlights the danger of only using a cutoff to establish endogenous levels compared with exogenous use of GHB in postmortem blood. PMID:25217550

  16. Establishing the volatile profile of pig carcasses as analogues for human decomposition during the early postmortem period.

    PubMed

    Armstrong, P; Nizio, K D; Perrault, K A; Forbes, S L

    2016-02-01

    Following a mass disaster, it is important that victims are rapidly located as the chances of survival decrease greatly after approximately 48 h. Urban search and rescue (USAR) teams may use a range of tools to assist their efforts but detector dogs still remain one of the most effective search tools to locate victims of mass disasters. USAR teams can choose to deploy human scent dogs (trained to locate living victims) or human remains detection (HRD) dogs (trained to locate deceased victims). However, little is known about the variation between live human scent and postmortem human remains scent and the timeframe during which one type of scent transitions to the other. The aim of the current study was to measure the change in the scent profile of human decomposition analogues during the first 72 h postmortem by measuring the volatile organic compounds (VOCs) that comprise the odour. Three pig carcasses (Sus scrofa domesticus L.) were placed on a soil surface and allowed to decompose under natural conditions. Decomposition odour was sampled frequently up to 75 h postmortem and analysed using comprehensive two-dimensional gas chromatography - time-of-flight mass spectrometry (GC×GC-TOFMS). A total of 105 postmortem VOCs were identified during the early postmortem period. The VOC profile during the early postmortem period was highly dynamic, changing both hourly and daily. A transition period was observed after 43 h postmortem, where the VOC profile appeared to shift from a distinct antemortem odour to a more generalised postmortem odour. These findings are important in informing USAR teams and their use of detector dogs for disaster victim recovery. PMID:27441249

  17. Postmortem findings and opportunistic infections in HIV-positive patients from a public hospital in Peru

    PubMed Central

    Eza, Dominique; Cerrillo, Gustavo; Moore, David A.J.; Castro, Cecilia; Ticona, Eduardo; Morales, Domingo; Cabanillas, Jose; Barrantes, Fernando; Alfaro, Alejandro; Benavides, Alejandro; Rafael, Arturo; Valladares, Gilberto; Arevalo, Fernando; Evans, Carlton A.; Gilman, Robert H.

    2010-01-01

    There is a paucity of HIV autopsy data from South America and none that document the postmortem findings in patients with HIV/AIDS in Peru. The purpose of this autopsy study was to determine the spectrum of opportunistic infections and the causes of mortality in HIV-positive patients at a public hospital in Lima. Clinico-epidemiological information regarding HIV infection in Peru is also reviewed. Sixteen HIV-related hospital postmortems, performed between 1999 and 2004, were included in this retrospective analysis. The primary cause of death was established in 12 patients: one died of neoplasia and 11 of infectious diseases, including 3 from pulmonary infection, 7 from disseminated infection, and 2 from central nervous system infection (one case had dual pathology). Opportunistic infections were identified in 14 cases, comprising cytomegalovirus, histoplasmosis, cryptococcosis, toxoplasmosis, Pneumocystis pneumonia, aspergillosis, tuberculosis, varicella zoster virus, and cryptosporidiosis. Fourteen patients had at least one AIDS-related disease that had been neither clinically suspected nor diagnosed premortem. Moreover, 82% of the diagnoses considered to be of important clinical significance had not been suspected antemortem. The spectrum and frequency of certain opportunistic infections differed from other South American autopsy studies, highlighting the importance of performing HIV/AIDS postmortems in resource-limited countries where locally specific disease patterns may be observed. PMID:16979302

  18. An initial investigation into the ecology of culturable aerobic postmortem bacteria.

    PubMed

    Chun, Lauren P; Miguel, Marcus J; Junkins, Emily N; Forbes, Shari L; Carter, David O

    2015-12-01

    Postmortem microorganisms are increasingly recognized for their potential to serve as physical evidence. Yet, we still understand little about the ecology of postmortem microbes, particularly those associated with the skin and larval masses. We conducted an experiment to characterize microbiological and chemical properties of decomposing swine (Sus scrofa domesticus) carcasses on the island of Oahu, Hawaii, USA, during June 2013. Bacteria were collected from the head, limb, and larval mass during the initial 145h of decomposition. We also measured the pH, temperature, and oxidation-reduction potential of larval masses in situ. Bacteria were cultured aerobically on Standard Nutrient Agar at 22°C and identified using protein or genetic signals. Carcass decomposition followed a typical sigmoidal pattern and associated bacterial communities differed by sampling location and time since death, although all communities were dominated by phyla Actinobacteria, Firmicutes, and Proteobacteria. Larval masses were reducing environments (~-200mV) of neutral pH (6.5-7.5) and high temperature (35°C-40°C). We recommend that culturable postmortem and larval mass microbiology and chemistry be investigated in more detail, as it has potential to complement culture-independent studies and serve as a rapid estimate of PMI. PMID:26654073

  19. Olanzapine-induced hyperglycemic ketoacidosis and corresponding acetone concentrations post-mortem: a forensic interpretation.

    PubMed

    House, Chris J

    2007-08-24

    Olanzapine has been shown to cause or have a contributory role in the development of hyperglycemia and diabetes mellitus. Without careful monitoring for the development of these conditions and control of the resulting adverse effects, patients receiving olanzapine may be at risk of developing fatal ketoacidosis. A review of post-mortem toxicological reports has revealed an increase in the incidence of post-mortem findings of acetone in decedents who were taking olanzapine over the past decade. A review of the current literature and a comprehensive review of case histories and toxicological findings were conducted at the Centre of Forensic Sciences (Toronto, Ontario). Olanzapine concentrations ranging from <62.5 to 858 ng/mL and acetone concentrations as high as 95 mg/dL were detected concurrently. Due to the unstable nature of olanzapine, in several instances quantitation was not possible despite elevated responses during qualitative screening procedures. Five cases suggesting olanzapine-induced ketoacidosis were identified based on the case history and toxicological findings. These data have been compiled and examined with respect to acetone concentrations following olanzapine use and the forensic relevance of post-mortem olanzapine and acetone concentrations are discussed. PMID:17084052

  20. The mincemeat postmortem: forensic aspects of World War II's boldest counterintelligence operation.

    PubMed

    Gottlieb, Klaus

    2009-01-01

    On the 30th of April 1943 the waterlogged body of Major William Martin of the Royal Marines drifted toward the shores of the Spanish Atlantic-coast city of Huelva after having been floated from a British submarine. A train of events was set into motion, which helped to change the course of the war. Major Martin, although dead, played a key role in the allied deception operation code-named Mincemeat. Operation Mincemeat has been the subject of several books and a motion picture. The crucial postmortem examination of Major Martin conducted by the Spanish authorities has received surprisingly little attention in the general intelligence literature and details of the medical aspects have to our knowledge never been examined. This article is, in a manner of speaking, a postmortem itself. The events happened 65 years ago and although new material is presented, the interpretation of its significance in the context of the known facts may convince some readers but not others. Nevertheless, we hope that this literary postmortem will fascinate intelligence and medical professionals alike and contribute to the medical and intelligence history of World War II. PMID:19216304

  1. Nonlesions, unusual cell types, and postmortem artifacts in the central nervous system of domestic animals.

    PubMed

    Wohlsein, P; Deschl, U; Baumgärtner, W

    2013-01-01

    In the central nervous system (CNS) of domestic animals, numerous specialized normal structures, unusual cell types, findings of uncertain or no significance, artifacts, and various postmortem alterations can be observed. They may cause confusion for inexperienced pathologists and those not specialized in neuropathology, leading to misinterpretations and wrong diagnoses. Alternatively, changes may mask underlying neuropathological processes. "Specialized structures" comprising the hippocampus and the circumventricular organs, including the vascular organ of the lamina terminalis, subfornical organ, subcommissural organ, pineal gland, median eminence/neurohypophyseal complex, choroid plexus, and area postrema, are displayed. Unusual cell types, including cerebellar external germinal cells, CNS progenitor cells, and Kolmer cells, are presented. In addition, some newly recognized cell types as of yet incompletely understood significance and functionality, such as synantocytes and aldynoglia, are introduced and described. Unusual reactive astrocytes in cats, central chromatolysis, neuronal vacuolation, spheroids, spongiosis, satellitosis, melanosis, neuromelanin, lipofuscin, polyglucosan bodies, and psammoma bodies may represent incidental findings of uncertain or no significance and should not be confused with significant microscopic changes. Auto- and heterolysis as well as handling and histotechnological processing may cause postmortem morphological changes of the CNS, including vacuolization, cerebellar conglutination, dark neurons, Buscaino bodies, freezing, and shrinkage artifacts, all of which have to be differentiated from genuine lesions. Postmortem invasion of micro-organisms should not be confused with intravital infections. Awareness of these different changes and their recognition are a prerequisite for identifying genuine lesions and may help to formulate a professional morphological and etiological diagnosis. PMID:22692622

  2. Four Postmortem Case Reports with Quantitative Detection of the Synthetic Cannabinoid, 5F-PB-22

    PubMed Central

    Behonick, George; Shanks, Kevin G.; Firchau, Dennis J.; Mathur, Gagan; Lynch, Charles F.; Nashelsky, Marcus; Jaskierny, David J.; Meroueh, Chady

    2014-01-01

    In January 2014, the US government temporarily designated 5F-PB-22, along with three other synthetic cannabinoids (AB-FUBINACA, ADB-PINACA and PB-22), into Schedule I. Over the course of a 4-month time period (July–October 2013), our laboratory quantitatively identified 5F-PB-22 in specimens obtained from four postmortem cases. We describe the four cases, to include pertinent autopsy findings and decedent histories, together with quantitative results for 5F-PB-22 determined in postmortem blood and antemortem serum. Samples were prepared via a liquid–liquid extraction at pH 10.2 into hexane : ethyl acetate. Instrumental analysis was achieved with liquid chromatography coupled with electrospray ionization tandem mass spectrometry operating in multiple reaction monitoring mode. Two ion transitions were monitored for the analyte of interest, and one ion transition was monitored for the internal standard. The observed concentration range of 5F-PB-22 is 1.1–1.5 ng/mL for three postmortem blood specimens and one antemortem serum specimen. Three of the decedents experienced abrupt, sudden death; however, one decedent expired after a rapidly deteriorating hospital course. PMID:24876364

  3. Four postmortem case reports with quantitative detection of the synthetic cannabinoid, 5F-PB-22.

    PubMed

    Behonick, George; Shanks, Kevin G; Firchau, Dennis J; Mathur, Gagan; Lynch, Charles F; Nashelsky, Marcus; Jaskierny, David J; Meroueh, Chady

    2014-10-01

    In January 2014, the US government temporarily designated 5F-PB-22, along with three other synthetic cannabinoids (AB-FUBINACA, ADB-PINACA and PB-22), into Schedule I. Over the course of a 4-month time period (July-October 2013), our laboratory quantitatively identified 5F-PB-22 in specimens obtained from four postmortem cases. We describe the four cases, to include pertinent autopsy findings and decedent histories, together with quantitative results for 5F-PB-22 determined in postmortem blood and antemortem serum. Samples were prepared via a liquid-liquid extraction at pH 10.2 into hexane : ethyl acetate. Instrumental analysis was achieved with liquid chromatography coupled with electrospray ionization tandem mass spectrometry operating in multiple reaction monitoring mode. Two ion transitions were monitored for the analyte of interest, and one ion transition was monitored for the internal standard. The observed concentration range of 5F-PB-22 is 1.1-1.5 ng/mL for three postmortem blood specimens and one antemortem serum specimen. Three of the decedents experienced abrupt, sudden death; however, one decedent expired after a rapidly deteriorating hospital course. PMID:24876364

  4. Postmortem serum protein growth arrest-specific 6 levels in sepsis-related deaths.

    PubMed

    Palmiere, Cristian; Augsburger, Marc

    2015-09-01

    Growth arrest-specific 6 (Gas6) is widely expressed in leukocytes, platelets, endothelial cells, and monocytes. It regulates various processes including granulocyte adhesion to the endothelium, cell migration, thrombus stabilization, and cytokine release. In humans, increased plasma Gas6 levels have been described in patients with sepsis and septic shock. In this study, Gas6 concentrations were measured in postmortem serum from femoral blood in a series of sepsis-related fatalities and control cases. The aims were twofold: first, to determine whether Gas6 can be reliably determined in postmortem serum; and second, to assess its diagnostic potential in identifying sepsis-related deaths. Two study groups were prospectively formed, a sepsis-related fatalities group (24 cases) and a control group (24 cases) including cases of deep vein thrombosis and fatal pulmonary embolism, cases of systemic inflammatory response syndrome in severe trauma, cases of end-stage renal failure, and cases of hanging (non-septic, non-SIRS, non-end stage renal failure cases). The preliminary results of this study seem to indicate that Gas6 can be effectively measured in postmortem serum. However, Gas6 levels in sepsis-related fatalities do not appear to be clearly distinguishable from concentrations in pulmonary embolism, severe trauma, and end-stage renal failure cases. These findings tend to support previous reports that indicated that Gas6 behaves as an acute phase reactant and can be considered a general marker of inflammation rather than a specific biomarker of sepsis. PMID:26233610

  5. Harms and responsibilities associated with battery-operated implants (BOI): who controls postmortem explantation?

    PubMed

    Bramstedt, Katrina A

    2013-01-01

    The postmortem issues raised by battery-operated implants (BOI) are complex and issues of consent, setting (clinical vs research), and environmental risks have received little attention in bioethics literature. Analyzing the issues, the following are argued: (1) Patients receiving BOIs should sign a consent form that includes a requirement for postmortem explant of the device; (2) BOI consent forms should require the explanted devices be returned to their manufacturers for Returned Product Analysis; (3) Failure to explant and analyze devices from the research setting fails the research goal of generation of knowledge for the benefit of future patients; (4) Failure to explant and analyze devices from the clinical setting allows product defects to be potentially hidden from patients, families, clinicians, manufacturers, and regulatory agencies; (5) Bodies buried with BOIs potentially harm the environment; (6) Religious or philosophical objections to autopsy should not supersede the duty to explant and analyze BOIs; (7) The concepts herein for BOIs could potentially extend to non-BOI if the device has failure modes that can lead to a potentially life-threatening event or can cause permanent debilitating health issues, and the burial or cremation of the device poses environmental harm. In these situations, neither the patient (premortem) nor family (postmortem) should have the right to refuse explant. PMID:23121647

  6. Fatal right coronary artery rupture following blunt chest trauma: detection by postmortem selective coronary angiography.

    PubMed

    Inokuchi, Go; Makino, Yohsuke; Motomura, Ayumi; Chiba, Fumiko; Torimitsu, Suguru; Hoshioka, Yumi; Iwase, Hirotaro

    2016-05-01

    Coronary artery injury is a rare complication following blunt chest trauma (BCT), and can be fatal. Here we report findings on postmortem selective coronary angiography of right coronary artery rupture after an assault involving blunt trauma to the chest. A woman in her 60s died after her son stomped on her chest. There were no appreciable signs of injury on external examination, and cause of death could not be determined by postmortem computed tomography (PMCT). Internal findings indicated that an external force had been applied to the anterior chest, as evidenced by subcutaneous hemorrhage and pericardial and cardiac contusions. Postmortem coronary angiography revealed irregularity of the intima and of the fat tissue surrounding the proximal part of the right coronary artery associated with a local filling defect. Histopathological examination suggested coronary rupture with dissection of the tunica media and compression of the lumen cavity. The key points in the present case are that no fatal injuries could be determined on external examination, and the heart and coronary artery injuries were not evident on PMCT. Criminality might be overlooked in such cases, as external investigation at the crime scene would be inadequate and could result in a facile diagnosis of cause of death. This is the first report of coronary artery rupture with dissection that was detected by CT coronary angiography, and provides helpful findings for reaching an appropriate decision both forensically and clinically. PMID:26126482

  7. Family override of valid donor consent to postmortem donation: issues in law and practice.

    PubMed

    Downie, J; Shea, A; Rajotte, C

    2008-06-01

    In 2005, 3974 Canadians were on waiting lists for organ transplants and 275 patients died while waiting. Canada's organ shortage has led to calls for changes to Canada's organ donation system and its legal framework. Herein we examine an issue in which law reform could both increase the number of available organs and better align practice with respect for autonomy, a core value underpinning the Canadian legal system: the issue of family overrides of a valid donor consent to postmortem donation. That is, we examine what should happen when an individual consented to postmortem donation but the family would like to override that consent. First, we examine the requirements for valid donor consent. Second, we consider the legal status of family overrides of valid donor consent in relation to postmortem donation. Third, we describe the available data with regard to the practice of permitting families to override valid donor consent and discuss the possible reasons for this practice. Finally, we describe and defend the desired results with respect to law reform and describe the actions needed to realize these results. PMID:18589083

  8. Detection of Human Bocavirus DNA by Multiplex PCR Analysis: Postmortem Case Report

    PubMed Central

    Ziyade, Nihan; Şirin, Gözde; Elgörmüş, Neval; Daş, Taner

    2015-01-01

    Background: Human bocavirus (HBoV) is a virus belonging to the Parvoviridae family, which has been newly discovered to be associated with respiratory tract infections in children. There are many reports worldwide on the endemicity of this virus. Since it is relatively new, it is not routinely detected in clinical laboratory investigations. Case Report: We demonstrated that HBoV infection caused the death of a 5-month-old girl with a history of high fever and wheezing. Human bocavirus (HBoV 1/2/3/4) was found in a nasopharyngeal swab, paraffin-embedded lung tissue and stool samples by multiplex PCR methods using postmortem microbiological analysis. Conclusion: This case suggests that lower respiratory tract infections due to HBoV may cause severe and life-threatening diseases. Postmortem microbiology is useful in both clinical and forensic autopsies, and allows a suspected infection to be confirmed. To our knowledge, this report is the first document of a HBoV postmortem case in Turkey. PMID:26167351

  9. [Techniques for preparing postmortem human eyes to perform anterior segment intraocular surgery].

    PubMed

    Vargas, L G; Werner, L; Pandey, S K; Werner, L P; Schmidbauer, J M; Zuleta, V; Escobar-Gómez, M; Apple, D J

    2003-02-01

    We describe different methods to prepare postmortem human or animal eyes used at the Center for Research in Ocular Therapeutics and Biodevices at the Storm Eye Institute, Medical University of South Carolina, Charleston, SC, USA. These techniques have been utilized for performing different surgical procedures (phacoemulsification, extracapsular cataract extraction, etc.), and for training of surgeons in-transition. Performing these techniques in the wet-laboratory contributed to improve surgical skills to perform the critical steps of the phacoemulsification surgery. Pathological evaluation of pseudophakic postmortem human eyes using the Miyake-Apple posterior view and histology was helpful to analyze postoperative complications of cataract surgery (anterior capsule opacification and posterior capsule opacification) secondary to postoperative proliferation of lens epithelial cells into the capsular bag. Modifications in the surgical techniques and/or lens design may be helpful to reduce these postoperative complications. Implantation of various aphakic and phakic intraocular lenses in postmortem human eyes as well as animal eyes was helpful to analyze the sizing and fitting of new lens designs within the eye. PMID:12647248

  10. Non-cell-autonomous postmortem lignification of tracheary elements in Zinnia elegans.

    PubMed

    Pesquet, Edouard; Zhang, Bo; Gorzsás, András; Puhakainen, Tuula; Serk, Henrik; Escamez, Sacha; Barbier, Odile; Gerber, Lorenz; Courtois-Moreau, Charleen; Alatalo, Edward; Paulin, Lars; Kangasjärvi, Jaakko; Sundberg, Björn; Goffner, Deborah; Tuominen, Hannele

    2013-04-01

    Postmortem lignification of xylem tracheary elements (TEs) has been debated for decades. Here, we provide evidence in Zinnia elegans TE cell cultures, using pharmacological inhibitors and in intact Z. elegans plants using Fourier transform infrared microspectroscopy, that TE lignification occurs postmortem (i.e., after TE programmed cell death). In situ RT-PCR verified expression of the lignin monomer biosynthetic cinnamoyl CoA reductase and cinnamyl alcohol dehydrogenase in not only the lignifying TEs but also in the unlignified non-TE cells of Z. elegans TE cell cultures and in living, parenchymatic xylem cells that surround TEs in stems. These cells were also shown to have the capacity to synthesize and transport lignin monomers and reactive oxygen species to the cell walls of dead TEs. Differential gene expression analysis in Z. elegans TE cell cultures and concomitant functional analysis in Arabidopsis thaliana resulted in identification of several genes that were expressed in the non-TE cells and that affected lignin chemistry on the basis of pyrolysis-gas chromatography/mass spectrometry analysis. These data suggest that living, parenchymatic xylem cells contribute to TE lignification in a non-cell-autonomous manner, thus enabling the postmortem lignification of TEs. PMID:23572543

  11. Utility of postmortem imaging system for anatomical education in skull base surgery.

    PubMed

    Kodera, Toshiaki; Arishima, Hidetaka; Kitai, Ryuhei; Kikuta, Ken-ichiro; Iino, Satoshi; Noriki, Sakon; Naiki, Hironobu

    2015-01-01

    Although cadaver dissections are important for skull base surgeons to acquire anatomical knowledge and techniques, their opportunities are limited in Japan. The Autopsy Imaging Center of the University of Fukui Hospital has both a CT scanner and an MR unit solely for deceased patients. The authors applied the postmortem imaging to cadaver dissections and evaluated its usefulness in surgical education. Ten sides of five formalin-fixed cadaver heads were dissected by ten neurosurgeons. Five neurosurgeons were young, three were moderately experienced, and two were experts in skull base surgery. They performed orbitozygomatic, anterior transpetrosal, posterior transpetrosal, and transcondylar approaches. CT bone images were taken before and after dissections, and MR images were taken before dissection to merge with the CT bone images. The usefulness of the images for each neurosurgeon and for each skull base approach was evaluated. The postmortem imaging system was useful for all neurosurgeons, especially in anterior transpetrosal, posterior transpetrosal, and transcondylar approaches. They could find the insufficiency or excessiveness of their drilling of specific bony structures with the images. Even the experts in skull base surgery could identify regions in which they could add drilling safely to widen the surgical field more. The postmortem imaging system was useful for skull base cadaver dissections. This system is expected to be utilized for education and research on surgical anatomy. PMID:25240531

  12. A Pathophysiological Insight into Sepsis and Its Correlation with Postmortem Diagnosis

    PubMed Central

    Pomara, C.; Riezzo, I.; Bello, S.; De Carlo, D.; Neri, M.; Turillazzi, E.

    2016-01-01

    Background. Sepsis is among the leading causes of death worldwide and is the focus of a great deal of attention from policymakers and caregivers. However, sepsis poses significant challenges from a clinical point of view regarding its early detection and the best organization of sepsis care. Furthermore, we do not yet have reliable tools for measuring the incidence of sepsis. Methods based on analyses of insurance claims are unreliable, and postmortem diagnosis is still challenging since autopsy findings are often nonspecific. Aim. The objective of this review is to assess the state of our knowledge of the molecular and biohumoral mechanisms of sepsis and to correlate them with our postmortem diagnosis ability. Conclusion. The diagnosis of sepsis-related deaths is an illustrative example of the reciprocal value of autopsy both for clinicians and for pathologists. A complete methodological approach, integrating clinical data by means of autopsy and histological and laboratory findings aiming to identify and demonstrate the host response to infectious insults, is mandatory to illuminate the exact cause of death. This would help clinicians to compare pre- and postmortem findings and to reliably measure the incidence of sepsis. PMID:27239102

  13. Equine parascarosis under the tropical weather conditions of Ethiopia: a coprological and postmortem study.

    PubMed

    Getachew, A M; Innocent, G T; Trawford, A F; Feseha, G; Reid, S J W; Love, S

    2008-02-01

    A cross-sectional coprological survey in the regions of Ada, Akaki, Bereh and Boset, and a retrospective postmortem investigation were conducted to study the epidemiology of Parascaris equorum in donkeys and horses in Ethiopia. Faecal samples from 803 working donkeys and 402 horses were collected, and the numbers of worms recovered from 112 donkeys examined postmortem between 1995 and 2004 were analysed. There was a high prevalence of infection and faecal egg output of P equorum in both donkeys and horses, and the severity of the infection in donkeys was increased irrespective of their age. The prevalence of the infection in the donkeys was 51.1 per cent and in the horses 16.2 per cent, and the prevalence in the donkeys examined postmortem was 55 per cent. There was no significant difference between different age groups of donkeys in either the prevalence or the intensity of the infection. The prevalence of the infection was significantly higher in the Ada and Akaki regions than in the Bereh and Boset regions. PMID:18263917

  14. Postmortem serum erythropoietin level as a marker of survival time in injury deaths.

    PubMed

    Quan, L; Zhu, B-L; Ishikawa, T; Michiue, T; Zhao, D; Ogawa, M; Maeda, H

    2010-07-15

    Circulating erythropoietin (EPO) is mainly derived from the kidneys, and the serum concentration is rapidly increased in response to anemia and hypoxia. The present study investigated postmortem serum EPO levels in injury death cases (n=185, postmortem time<48 h, survival time <7 days: sharp instrument injury, n=44 and blunt injury, n=141) with regard to survival time, compared with C-reactive protein (CRP) as a marker of inflammation. Serum levels of both markers were independent of postmortem time. A survival time-dependent increase in serum EPO up to about 100 mU/ml was seen within 6h of sharp instrument injury to the heart or a proximal major vessel (thoracic aorta or subclavian/carotid artery) and blunt injury with massive hemorrhages, showing high correlations (r=0.957 and r=0.822, respectively, P<0.0001), whereas the increase was insignificant (P>0.05) for sharp instrument injury to a peripheral vessel or lungs/abdominal viscera and blunt injury with minor hemorrhages over the same survival period. A further increase (>100 mU/ml) was often detected in cases of death about 24h after blunt injury, irrespective of the type of injury. In contrast, a gradual increase in serum CRP level was seen about 12-24h after blunt injury. These findings suggest that serum EPO can be a marker for investigating survival time within 6h of major injury involving acute massive hemorrhaging. PMID:20430543

  15. Non-Cell-Autonomous Postmortem Lignification of Tracheary Elements in Zinnia elegans[W][OA

    PubMed Central

    Pesquet, Edouard; Zhang, Bo; Gorzsás, András; Puhakainen, Tuula; Serk, Henrik; Escamez, Sacha; Barbier, Odile; Gerber, Lorenz; Courtois-Moreau, Charleen; Alatalo, Edward; Paulin, Lars; Kangasjärvi, Jaakko; Sundberg, Björn; Goffner, Deborah; Tuominen, Hannele

    2013-01-01

    Postmortem lignification of xylem tracheary elements (TEs) has been debated for decades. Here, we provide evidence in Zinnia elegans TE cell cultures, using pharmacological inhibitors and in intact Z. elegans plants using Fourier transform infrared microspectroscopy, that TE lignification occurs postmortem (i.e., after TE programmed cell death). In situ RT-PCR verified expression of the lignin monomer biosynthetic cinnamoyl CoA reductase and cinnamyl alcohol dehydrogenase in not only the lignifying TEs but also in the unlignified non-TE cells of Z. elegans TE cell cultures and in living, parenchymatic xylem cells that surround TEs in stems. These cells were also shown to have the capacity to synthesize and transport lignin monomers and reactive oxygen species to the cell walls of dead TEs. Differential gene expression analysis in Z. elegans TE cell cultures and concomitant functional analysis in Arabidopsis thaliana resulted in identification of several genes that were expressed in the non-TE cells and that affected lignin chemistry on the basis of pyrolysis–gas chromatography/mass spectrometry analysis. These data suggest that living, parenchymatic xylem cells contribute to TE lignification in a non-cell-autonomous manner, thus enabling the postmortem lignification of TEs. PMID:23572543

  16. Postmortem degradation of skeletal muscle proteins: a novel approach to determine the time since death.

    PubMed

    Pittner, Stefan; Monticelli, Fabio C; Pfisterer, Alexander; Zissler, Angela; Sänger, Alexandra M; Stoiber, Walter; Steinbacher, Peter

    2016-03-01

    Estimating the time since death is a very important aspect in forensic sciences which is pursued by a variety of methods. The most precise method to determine the postmortem interval (PMI) is the temperature method which is based on the decrease of the body core temperature from 37 °C. However, this method is only useful in the early postmortem phase (~0-36 h). The aim of the present work is to develop an accurate method for PMI determination beyond this present limit. For this purpose, we used sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE), Western blotting, and casein zymography to analyze the time course of degradation of selected proteins and calpain activity in porcine biceps femoris muscle until 240 h postmortem (hpm). Our results demonstrate that titin, nebulin, desmin, cardiac troponin T, and SERCA1 degraded in a regular and predictable fashion in all samples investigated. Similarly, both the native calpain 1 and calpain 2 bands disintegrate into two bands subsequently. This degradation behavior identifies muscular proteins and enzymes as promising substrates for future molecular-based PMI determination technologies. PMID:26041514

  17. Epigenetics in the Human Brain

    PubMed Central

    Houston, Isaac; Peter, Cyril J; Mitchell, Amanda; Straubhaar, Juerg; Rogaev, Evgeny; Akbarian, Schahram

    2013-01-01

    Many cellular constituents in the human brain permanently exit from the cell cycle during pre- or early postnatal development, but little is known about epigenetic regulation of neuronal and glial epigenomes during maturation and aging, including changes in mood and psychosis spectrum disorders and other cognitive or emotional disease. Here, we summarize the current knowledge base as it pertains to genome organization in the human brain, including the regulation of DNA cytosine methylation and hydroxymethylation, and a subset of (altogether >100) residue-specific histone modifications associated with gene expression, and silencing and various other functional chromatin states. We propose that high-resolution mapping of epigenetic markings in postmortem brain tissue or neural cultures derived from induced pluripotent cells (iPS), in conjunction with transcriptome profiling and whole-genome sequencing, will increasingly be used to define the molecular pathology of specific cases diagnosed with depression, schizophrenia, autism, or other major psychiatric disease. We predict that these highly integrative explorations of genome organization and function will provide an important alternative to conventional approaches in human brain studies, which mainly are aimed at uncovering group effects by diagnosis but generally face limitations because of cohort size. PMID:22643929

  18. Effect of ultimate pH on postmortem myofibrillar protein degradation and meat quality characteristics of Chinese Yellow crossbreed cattle.

    PubMed

    Li, Peng; Wang, Tiantian; Mao, Yanwei; Zhang, Yimin; Niu, Lebao; Liang, Rongrong; Zhu, Lixian; Luo, Xin

    2014-01-01

    This paper describes the complex effects of postmortem ultimate pH (pHu) on Chinese Yellow crossbreed cattle quality during postmortem ageing and provides an explanation of how pHu affects beef tenderness. High pHu beef had the highest initial tenderness (P < 0.05) compared with other groups at 1 day postmortem. Intermediate and low pHu beef had similar initial WBSF at 1 day postmortem, but intermediate pHu beef had slower tenderization rate than low pHu beef (P < 0.05). Purge loss, cooking loss, L*, a*, and b* values decreased with increasing pHu during ageing (P < 0.05). Myofibril fragmentation index (MFI) was higher in high pHu beef than intermediate and low pHu beef throughout ageing (P < 0.05). Protein degradation studies found that desmin and troponin-T appeared degraded within 0.5 h postmortem for high and low pHu beef, compared to >2 days for intermediate pHu beef. Overall, Chinese Yellow crossbred cattle tenderness is related to pHu, which may be affected by proteolytic enzymatic activity. Therefore, pHu may be used to predict beef tenderness and other quality characteristics during postmortem ageing. To achieve consistent tenderness, different ageing times should be used, depending on pHu. PMID:25197695

  19. Effect of Ultimate pH on Postmortem Myofibrillar Protein Degradation and Meat Quality Characteristics of Chinese Yellow Crossbreed Cattle

    PubMed Central

    Wang, Tiantian; Mao, Yanwei; Zhang, Yimin; Niu, Lebao; Liang, Rongrong; Zhu, Lixian; Luo, Xin

    2014-01-01

    This paper describes the complex effects of postmortem ultimate pH (pHu) on Chinese Yellow crossbreed cattle quality during postmortem ageing and provides an explanation of how pHu affects beef tenderness. High pHu beef had the highest initial tenderness (P < 0.05) compared with other groups at 1 day postmortem. Intermediate and low pHu beef had similar initial WBSF at 1 day postmortem, but intermediate pHu beef had slower tenderization rate than low pHu beef (P < 0.05). Purge loss, cooking loss, L*, a*, and b* values decreased with increasing pHu during ageing (P < 0.05). Myofibril fragmentation index (MFI) was higher in high pHu beef than intermediate and low pHu beef throughout ageing (P < 0.05). Protein degradation studies found that desmin and troponin-T appeared degraded within 0.5 h postmortem for high and low pHu beef, compared to >2 days for intermediate pHu beef. Overall, Chinese Yellow crossbred cattle tenderness is related to pHu, which may be affected by proteolytic enzymatic activity. Therefore, pHu may be used to predict beef tenderness and other quality characteristics during postmortem ageing. To achieve consistent tenderness, different ageing times should be used, depending on pHu. PMID:25197695

  20. Ontogenetic Shape Change in the Chicken Brain: Implications for Paleontology

    PubMed Central

    Kawabe, Soichiro; Matsuda, Seiji; Tsunekawa, Naoki; Endo, Hideki

    2015-01-01

    Paleontologists have investigated brain morphology of extinct birds with little information on post-hatching changes in avian brain morphology. Without the knowledge of ontogenesis, assessing brain morphology in fossil taxa could lead to misinterpretation of the phylogeny or neurosensory development of extinct species. Hence, it is imperative to determine how avian brain morphology changes during post-hatching growth. In this study, chicken brain shape was compared at various developmental stages using three-dimensional (3D) geometric morphometric analysis and the growth rate of brain regions was evaluated to explore post-hatching morphological changes. Microscopic MRI (μMRI) was used to acquire in vivo data from living and post-mortem chicken brains. The telencephalon rotates caudoventrally during growth. This change in shape leads to a relative caudodorsal rotation of the cerebellum and myelencephalon. In addition, all brain regions elongate rostrocaudally and this leads to a more slender brain shape. The growth rates of each brain region were constant and the slopes from the growth formula were parallel. The dominant pattern of ontogenetic shape change corresponded with interspecific shape changes due to increasing brain size. That is, the interspecific and ontogenetic changes in brain shape due to increased size have similar patterns. Although the shape of the brain and each brain region changed considerably, the volume ratio of each brain region did not change. This suggests that the brain can change its shape after completing functional differentiation of the brain regions. Moreover, these results show that consideration of ontogenetic changes in brain shape is necessary for an accurate assessment of brain morphology in paleontological studies. PMID:26053849

  1. Ontogenetic Shape Change in the Chicken Brain: Implications for Paleontology.

    PubMed

    Kawabe, Soichiro; Matsuda, Seiji; Tsunekawa, Naoki; Endo, Hideki

    2015-01-01

    Paleontologists have investigated brain morphology of extinct birds with little information on post-hatching changes in avian brain morphology. Without the knowledge of ontogenesis, assessing brain morphology in fossil taxa could lead to misinterpretation of the phylogeny or neurosensory development of extinct species. Hence, it is imperative to determine how avian brain morphology changes during post-hatching growth. In this study, chicken brain shape was compared at various developmental stages using three-dimensional (3D) geometric morphometric analysis and the growth rate of brain regions was evaluated to explore post-hatching morphological changes. Microscopic MRI (μMRI) was used to acquire in vivo data from living and post-mortem chicken brains. The telencephalon rotates caudoventrally during growth. This change in shape leads to a relative caudodorsal rotation of the cerebellum and myelencephalon. In addition, all brain regions elongate rostrocaudally and this leads to a more slender brain shape. The growth rates of each brain region were constant and the slopes from the growth formula were parallel. The dominant pattern of ontogenetic shape change corresponded with interspecific shape changes due to increasing brain size. That is, the interspecific and ontogenetic changes in brain shape due to increased size have similar patterns. Although the shape of the brain and each brain region changed considerably, the volume ratio of each brain region did not change. This suggests that the brain can change its shape after completing functional differentiation of the brain regions. Moreover, these results show that consideration of ontogenetic changes in brain shape is necessary for an accurate assessment of brain morphology in paleontological studies. PMID:26053849

  2. Leading Change, Adding Value.

    PubMed

    Evans, Nick

    2016-09-12

    Essential facts Leading Change, Adding Value is NHS England's new nursing and midwifery framework. It is designed to build on Compassion in Practice (CiP), which was published 3 years ago and set out the 6Cs: compassion, care, commitment, courage, competence and communication. CiP established the values at the heart of nursing and midwifery, while the new framework sets out how staff can help transform the health and care sectors to meet the aims of the NHS England's Five Year Forward View. PMID:27615573

  3. Post-mortem findings and piglet mortality in relation to strategic use of straw at farrowing.

    PubMed

    Westin, Rebecka; Holmgren, Nils; Hultgren, Jan; Ortman, Kerstin; Linder, Anders; Algers, Bo

    2015-05-01

    Piglet survival is the outcome of complex interactions between the sow, the piglet and their environment. In order to facilitate nest-building and to provide a suitable environment for the newborn piglets, a strategic method to supply loose housed sows with large quantities of straw at farrowing has been developed by Swedish piglet-producing farmers. The objectives of this cohort study were to use post-mortem findings to assess the causes of death and to quantify the effect of a large quantity of straw provided before farrowing compared to limited small daily amounts on stillbirths, post-mortem findings in piglets dying within 5 days after birth and the pre-weaning mortality. On each of four commercial piglet-producing farms in South-West Sweden, one batch of sows was studied during two consecutive lactations. At inclusion, sows were randomly assigned to two treatment groups, and sows remaining in the batch during the next lactation switched treatment group. In the STRAW group (n=181 litters) sows were provided with 15-20 kg of chopped straw 2 days prior to the calculated date of farrowing. Sows in the CONTROL group (n=182 litters) received 0.5-1 kg of chopped straw on a daily basis plus about 2 kg for nest-building when the stockperson judged the sow to be about to farrow. After onset of farrowing, additionally 1-2 kg was given. Post-mortem examination was performed in all piglets that died within 5 days after birth (n=798). The three major post-mortem findings were starvation (34%) crushing by the sow (28%), and enteritis (24%). In conclusion, strategic use of large quantities of straw reduced the number of stillborn piglets per litter by 27% (p=0.007). Under the conditions studied, the pre-weaning mortality of liveborn piglets was not affected by treatment; however, the distribution of post-mortem findings differed with fewer piglets dying due to starvation and more due to crushing and enteritis in STRAW litters. PMID:25792335

  4. Brain Tumors

    MedlinePlus

    A brain tumor is a growth of abnormal cells in the tissues of the brain. Brain tumors can be benign, with no cancer cells, ... cancer cells that grow quickly. Some are primary brain tumors, which start in the brain. Others are ...

  5. Postmortem diagnosis of cytomegalovirus and accompanying other infection agents by real-time PCR in cases of sudden unexpected death in infancy (SUDI).

    PubMed

    Yagmur, Gulhan; Ziyade, Nihan; Elgormus, Neval; Das, Taner; Sahin, M Feyzi; Yildirim, Muzaffer; Ozgun, Ayse; Akcay, Arzu; Karayel, Ferah; Koc, Sermet

    2016-02-01

    As an opportunistic pathogen with high mortality rates, Cytomegalovirus (CMV) may lead to fatal disseminated CMV infection of the premature and newborn; thus necessitating the demonstration of CMV-DNA with clinical history and/or histopathological findings of CMV infection and defining other bacterial and viral infection agents with real-time polymerase chain reaction (RT-PCR) in udden unexpected death in infancy (SUDI) cases as we aimed in this study. 314 (144 female, 170 male) SUDI cases were prospectively investigated from January 2013 to January 2015 in Istanbul Forensic Medicine Institution. The study includes 87 tissue samples of 39 cases for post-mortem histopathological examination of interstitial pneumonia, myocarditis, meningitis, encephalitis, hepatitis, colitis or tubulointerstitial nephritis and/or accompanying chronic sialadenitis. CMV-DNA was found positive in 35 (40.2%) salivary gland, 19 (21.8%) lung, 1 (1.1%) tonsil, and 1 (1.1%) brain tissues. CMV sialadenitis and/or CMV pneumonia associated with other viral and/or bacterial agents were detected in 23 (60%) of 39 infant cases. The demonstration of CMV-DNA would significantly clarify the cause of death and collection of epidemiological data in SUDI cases with clinical history and histopathological findings of CMV infection accompanying chronic CMV sialadenitis. Furthermore, CMV suppresses the immune system, and may predispose to other bacterial and/or viral infections in these cases. Post-mortem molecular investigations are useful in explaining cause of death in SUDI with a suspicion of infection in forensic autopsies. PMID:26694873

  6. Post-mortem findings in southern right whales Eubalaena australis at Península Valdés, Argentina, 2003-2012.

    PubMed

    McAloose, Denise; Rago, M Virginia; Di Martino, Matías; Chirife, Andrea; Olson, Sarah H; Beltramino, Lucas; Pozzi, Luciana M; Musmeci, Luciana; La Sala, Luciano; Mohamed, Nadia; Sala, Juan Emilio; Bandieri, Lucas; Andrejuk, Julian; Tomaszewicz, Ania; Seimon, Tracie; Sironi, Mariano; Samartino, Luis E; Rowntree, Victoria; Uhart, Marcela M

    2016-04-12

    Between 2003 and 2012, 605 southern right whales (SRW; Eubalaena australis) were found dead along the shores of Península Valdés (PV), Argentina. These deaths included alarmingly high annual losses between 2007 and 2012, a peak number of deaths (116) in 2012, and a significant number of deaths across years in calves-of-the-year (544 of 605 [89.9%]; average = 60.4 yr(-1)). Post-mortem examination and pathogen testing were performed on 212 whales; 208 (98.1%) were calves-of-the-year and 48.0% of these were newborns or neonates. A known or probable cause of death was established in only a small number (6.6%) of cases. These included ship strike in a juvenile and blunt trauma or lacerations (n = 5), pneumonia (n = 4), myocarditis (n = 2), meningitis (n = 1), or myocarditis and meningitis (n = 1) in calves. Ante-mortem gull parasitism was the most common gross finding. It was associated with systemic disease in a single 1-2 mo old calf. Immunohistochemical labeling for canine distemper virus, Toxoplasma gondii and Brucella spp., and PCR for cetacean morbillivirus (CeMV), influenza A, and apicomplexan protozoa were negative on formalin-fixed, paraffin-embedded lung and brain samples from a subset of whales; PCR for Brucella spp. was positive in a newborn/neonate with pneumonia. Skin samples from whales with gull parasitism were PCR negative for CeMV, poxvirus, and papillomavirus. This is the first long-term study to investigate and summarize notable post-mortem findings in the PV SRW population. Consistent, significant findings within or between years to explain the majority of deaths and those in high-mortality years remain to be identified. PMID:27068500

  7. Redox changes in cat brain cytochrome-c oxidase after blood-fluorocarbon exchange.

    PubMed

    Ferrari, M; Hanley, D F; Wilson, D A; Traystman, R J

    1990-06-01

    Rapid scanning near-infrared spectroscopy (730-960 nm) was utilized to determine cat brain cytochrome-c oxidase copper band by blood-perfluorochemical emulsion (Oxypherol) exchange. Spectra were carried out before, during, and after the exchange transfusion on animals with preserved somatosensory-evoked potentials and microsphere-determined cerebral blood flow. Remaining hemoglobin (less than 4% of control) was converted to carboxyhemoglobin that does not absorb in this spectral region. Difference spectra, between an hypercapnic status (8% CO2-92% O2) and postmortem, demonstrated the presence of a broad absorption band centered around 820-845 nm that could be attributed to the oxidized low potential copper ion (CuA) of cytochrome-c oxidase. However, we were unable to further oxidize this band by adding CO2 to the inspired gas mixture, but this inconsistency may be due to the near-maximal cerebral blood flow levels present in this preparation. Cytochrome oxidation by CO2 is normally attributed to increased O2 delivery to the tissue, secondary to an increased cerebral perfusion. We were unable to induce further increases in cerebral blood flow. In contrast, the cytochrome band could be reduced both by lowering fractional O2 concentration and by inducing circulatory arrest. The spectral data support the hypothesis that it is possible to quantify the cytochrome-c oxidase copper band in the near-infrared spectral region. PMID:2163218

  8. Regulation of neurotropic signaling by the inducible, NF-kB-sensitive miRNA-125b in Alzheimer's disease (AD) and in primary human neuronal-glial (HNG) cells.

    PubMed

    Zhao, Yuhai; Bhattacharjee, Surjyadipta; Jones, Brandon M; Hill, Jim; Dua, Prerna; Lukiw, Walter J

    2014-08-01

    Inducible microRNAs (miRNAs) perform critical regulatory roles in central nervous system (CNS) development, aging, health, and disease. Using miRNA arrays, RNA sequencing, enhanced Northern dot blot hybridization technologies, Western immunoblot, and bioinformatics analysis, we have studied miRNA abundance and complexity in Alzheimer's disease (AD) brain tissues compared to age-matched controls. In both short post-mortem AD and in stressed primary human neuronal-glial (HNG) cells, we observe a consistent up-regulation of several brain-enriched miRNAs that are under transcriptional control by the pro-inflammatory transcription factor NF-kB. These include miRNA-9, miRNA-34a, miRNA-125b, miRNA-146a, and miRNA-155. Of the inducible miRNAs in this subfamily, miRNA-125b is among the most abundant and significantly induced miRNA species in human brain cells and tissues. Bioinformatics analysis indicated that an up-regulated miRNA-125b could potentially target the 3'untranslated region (3'-UTR) of the messenger RNA (mRNA) encoding (a) a 15-lipoxygenase (15-LOX; ALOX15; chr 17p13.3), utilized in the conversion of docosahexaneoic acid into neuroprotectin D1 (NPD1), and (b) the vitamin D3 receptor (VDR; VD3R; chr12q13.11) of the nuclear hormone receptor superfamily. 15-LOX and VDR are key neuromolecular factors essential in lipid-mediated signaling, neurotrophic support, defense against reactive oxygen and nitrogen species (reactive oxygen and nitrogen species), and neuroprotection in the CNS. Pathogenic effects appear to be mediated via specific interaction of miRNA-125b with the 3'-UTR region of the 15-LOX and VDR messenger RNAs (mRNAs). In AD hippocampal CA1 and in stressed HNG cells, 15-LOX and VDR down-regulation and a deficiency in neurotrophic support may therefore be explained by the actions of a single inducible, pro-inflammatory miRNA-125b. We will review the recent data on the pathogenic actions of this up-regulated miRNA-125b in AD and discuss potential

  9. Regulation of neurotropic signaling by the inducible, NF-kB-sensitive miRNA-125b in Alzheimer’s disease (AD) and in primary human neuronal-glial (HNG) cells

    PubMed Central

    Zhao, Yuhai; Bhattacharjee, Surjyadipta; Jones, Brandon M.; Hill, Jim; Dua, Prerna; Lukiw, Walter J.

    2014-01-01

    Inducible micro RNAs (miRNAs) perform critical regulatory roles in central nervous system (CNS) development, aging, health and disease. Using miRNA arrays, RNA-sequencing, enhanced Northern dot blot hybridization technologies, Western immunoblot and bioinformatics analysis we have studied miRNA abundance and complexity in Alzheimer’s disease (AD) brain tissues compared to age-matched controls. In both short post-mortem AD and in stressed primary human neuronal-glial (HNG) cells we observe a consistent up-regulation of several brain-enriched miRNAs that are under transcriptional control by the pro-inflammatory transcription factor NF-kB. These include miRNA-9, miRNA-34a, miRNA-125b, miRNA-146a and miRNA-155. Of the inducible miRNAs in this subfamily, miRNA-125b is amongst the most abundant and significantly induced miRNA species in human brain cells and tissues. Bioinformatics analysis indicates that up-regulated miRNA-125b targeted expression of (a) the 15-lipoxygenase (15-LOX; ALOX15; chr 17p13.3), utilized in the conversion of docosa-hexaneoic acid (DHA) into neuroprotectin D1 (NPD1), and (b) the vitamin D3 receptor (VDR; VD3R; chr12q13.11) of the nuclear hormone receptor superfamily. 15-LOX and VDR are key neuromolecular factors essential in lipid-mediated signaling, neurotrophic support, defense against reactive oxygen and nitrogen species (ROS, RNS) and neuroprotection in the CNS. Pathogenic effects appear to be mediated via specific interaction of miRNA-125b with the 3′-untranslated region (3′-UTR) of the 15-LOX and VDR messenger RNAs (mRNAs). In AD hippocampal CA1 and in stressed HNG cells, 15-LOX and VDR down-regulation and a deficiency in neurotrophic support, may therefore be explained by the actions of a single inducible, pro-inflammatory miRNA-125b. We will review recent data on the pathogenic actions of this up-regulated miRNA-125b in AD, and discuss potential therapeutic approaches using either anti-NF-kB or anti-miRNA-125b strategies. These may

  10. Dirac operator on fuzzy AdS2

    NASA Astrophysics Data System (ADS)

    Fakhri, Hossein; Imaanpur, Ali

    2003-03-01

    In this article we construct the chirality and Dirac operators on noncommutative AdS2. We also derive the discrete spectrum of the Dirac operator which is important in the study of the spectral triple associated to AdS2. It is shown that the degeneracy of the spectrum present in the commutative AdS2 is lifted in the noncommutative case. The way we construct the chirality operator is suggestive of how to introduce the projector operators of the corresponding projective modules on this space.

  11. An xp model on AdS2 spacetime

    NASA Astrophysics Data System (ADS)

    Molina-Vilaplana, Javier; Sierra, Germán

    2013-12-01

    In this paper we formulate the xp model on the AdS2 spacetime. We find that the spectrum of the Hamiltonian has positive and negative eigenvalues, whose absolute values are given by a harmonic oscillator spectrum, which in turn coincides with that of a massive Dirac fermion in AdS2. We extend this result to generic xp models which are shown to be equivalent to a massive Dirac fermion on spacetimes whose metric depend of the xp Hamiltonian. Finally, we construct the generators of the isometry group SO(2,1) of the AdS2 spacetime, and discuss the relation with conformal quantum mechanics.

  12. Aromatase Expression in the Hippocampus of AD Patients and 5xFAD Mice

    PubMed Central

    Prange-Kiel, Janine; Dudzinski, Danuta A.; Pröls, Felicitas; Glatzel, Markus; Matschke, Jakob; Rune, Gabriele M.

    2016-01-01

    Numerous studies show that 17β-estradiol (E2) protects against Alzheimer's disease (AD) induced neurodegeneration. The E2-synthesizing enzyme aromatase is expressed in healthy hippocampi, but although the hippocampus is severely affected in AD, little is known about the expression of hippocampal aromatase in AD. To better understand the role of hippocampal aromatase in AD, we studied its expression in postmortem material from patients with AD and in a mouse model for AD (5xFAD mice). In human hippocampi, aromatase-immunoreactivity was observed in the vast majority of principal neurons and signal quantification revealed higher expression of aromatase protein in AD patients compared to age- and sex-matched controls. The tissue-specific first exons of aromatase I.f, PII, I.3, and I.6 were detected in hippocampi of controls and AD patients by RT-PCR. In contrast, 3-month-old, female 5xFAD mice showed lower expression of aromatase mRNA and protein (measured by qRT-PCR and semiquantitative immunohistochemistry) than WT controls; no such differences were observed in male mice. Our findings stress the importance of hippocampal aromatase expression in neurodegenerative diseases. PMID:27298742

  13. Post-mortem levels and tissue distribution of codeine, codeine-6-glucuronide, norcodeine, morphine and morphine glucuronides in a series of codeine-related deaths.

    PubMed

    Frost, Joachim; Løkken, Trine Nordgård; Helland, Arne; Nordrum, Ivar Skjåk; Slørdal, Lars

    2016-05-01

    This article presents levels and tissue distribution of codeine, codeine-6-glucuronide (C6G), norcodeine, morphine and the morphine metabolites morphine-3-glucuronide (M3G) and morphine-6-glucuronide (M6G) in post-mortem blood (peripheral and heart blood), vitreous fluid, muscle, fat and brain tissue in a series of 23 codeine-related fatalities. CYP2D6 genotype is also determined and taken into account. Quantification of codeine, C6G, norcodeine, morphine, M3G and M6G was performed with a validated solid phase extraction LC-MS method. The series comprise 19 deaths (83%) attributed to mixed drug intoxication, 4 deaths (17%) attributed to other causes of death, and no cases of unambiguous monointoxication with codeine. The typical peripheral blood concentration pattern in individual cases was C6G≫codeine≫norcodeine>morphine, and M3G>M6G>morphine. In matrices other than blood, the concentration pattern was similar, although in a less systematic fashion. Measured concentrations were generally lower in matrices other than blood, especially in brain and fat, and in particular for the glucuronides (C6G, M3G and M6G) and, to some extent, morphine. In brain tissue, the presumed active moieties morphine and M6G were both below the LLOQ (0.0080mg/L and 0.058mg/L, respectively) in a majority of cases. In general, there was a large variability in both measured concentrations and calculated blood/tissue concentration ratios. There was also a large variability in calculated ratios of morphine to codeine, C6G to codeine and norcodeine to codeine in all matrices, and CYP2D6 genotype was not a reliable predictor of these ratios. The different blood/tissue concentration ratios showed no systematic relationship with the post-mortem interval. No coherent degradation or formation patterns for codeine, morphine, M3G and M6G were observed upon reanalysis in peripheral blood after storage. PMID:26986973

  14. Early AD pathology in a [C-11]PiB-negative case: a PiB-amyloid imaging, biochemical, and immunohistochemical study

    PubMed Central

    Abrahamson, Eric E.; Price, Julie C.; Hamilton, Ronald L.; Mathis, Chester A.; Paljug, William R.; Debnath, Manik L.; Cohen, Anne D.; Mizukami, Katsuyoshi; DeKosky, Steven T.; Lopez, Oscar L.; Klunk, William E.

    2012-01-01

    Amyloid-β (Aβ) deposits are detectable in the brain in vivo using positron emission tomography (PET) and [C-11]-labeled Pittsburgh Compound B ([C-11]PiB); however, the sensitivity of this technique is not well understood. In this study, we examined Aβ pathology in an individual who had clinical diagnoses of probable dementia with Lewy bodies and possible Alzheimer’s disease (AD) but with no detectable [C-11]PiB PET retention ([C-11]PiB(−)) when imaged 17 months prior to death. Brain samples were processed in parallel with region-matched samples from an individual with a clinical diagnosis of probable AD and a positive [C-11]PiB PET scan ([C-11]PiB(+)) when imaged 10 months prior to death. In the [C-11]PiB(−) case, Aβ plaques were sparse, occupying less than 2% cortical area, and were weakly labeled with 6-CN-PiB, a highly fluorescent derivative of PiB. In contrast, Aβ plaques occupied up to 12% cortical area in the [C-11]PiB(+) case, and were intensely labeled with 6-CN-PIB. The [C-11]PiB(−) case had low levels of [H-3]PiB binding (<100 pmol/g) and Aβ1–42 (<500 pmol/g) concentration except in the frontal cortex where Aβ1–42 values (788 pmol/g) approached cortical values in the [C-11]PiB(+) case (800–1,700 pmol/g). In several cortical regions of the [C-11]PiB(−) case, Aβ1–40 levels were within the range of cortical Aβ1–40 values in the [C-11]PiB(+) case. Antemortem [C-11]PiB DVR values correlated well with region-matched postmortem measures of Aβ1–42 and Aβ1–40 in the [C-11]PiB(+), and with Aβ1–42 only in the [C-11]PiB(−) case. The low ratios of [H-3]PiB binding levels to Aβ concentrations and 6-CN-PiB to Aβ plaque loads in the [C-11]PiB(−) case indicate that Aβ pathology in the brain may be associated with low or undetectable levels of [C-11]PiB retention. Studies in greater numbers of [C-11]PiB PET autopsy cases are needed to define the Aβ concentration and [H-3]PiB binding levels required to produce a positive [C-11

  15. Do glutathione levels decline in aging human brain?

    PubMed

    Tong, Junchao; Fitzmaurice, Paul S; Moszczynska, Anna; Mattina, Katie; Ang, Lee-Cyn; Boileau, Isabelle; Furukawa, Yoshiaki; Sailasuta, Napapon; Kish, Stephen J

    2016-04-01

    For the past 60 years a major theory of "aging" is that age-related damage is largely caused by excessive uncompensated oxidative stress. The ubiquitous tripeptide glutathione is a major antioxidant defense mechanism against reactive free radicals and has also served as a marker of changes in oxidative stress. Some (albeit conflicting) animal data suggest a loss of glutathione in brain senescence, which might compromise the ability of the aging brain to meet the demands of oxidative stress. Our objective was to establish whether advancing age is associated with glutathione deficiency in human brain. We measured reduced glutathione (GSH) levels in multiple regions of autopsied brain of normal subjects (n=74) aged one day to 99 years. Brain GSH levels during the infancy/teenage years were generally similar to those in the oldest examined adult group (76-99 years). During adulthood (23-99 years) GSH levels remained either stable (occipital cortex) or increased (caudate nucleus, frontal and cerebellar cortices). To the extent that GSH levels represent glutathione antioxidant capacity, our postmortem data suggest that human brain aging is not associated with declining glutathione status. We suggest that aged healthy human brains can maintain antioxidant capacity related to glutathione and that an age-related increase in GSH levels in some brain regions might possibly be a compensatory response to increased oxidative stress. Since our findings, although suggestive, suffer from the generic limitations of all postmortem brain studies, we also suggest the need for "replication" investigations employing the new (1)H MRS imaging procedures in living human brain. PMID:26845616

  16. Brain abscess

    MedlinePlus

    Brain abscesses commonly occur when bacteria or fungi infect part of the brain. As a result, swelling and irritation (inflammation) develop. Infected brain cells, white blood cells, live and dead bacteria, ...

  17. Brain Tumors

    MedlinePlus

    ... brain. Brain tumors can be benign, with no cancer cells, or malignant, with cancer cells that grow quickly. Some are primary brain ... targeted therapy. Targeted therapy uses substances that attack cancer cells without harming normal cells. Many people get ...

  18. Brain components

    MedlinePlus Videos and Cool Tools

    The brain is composed of more than a thousand billion neurons. Specific groups of them, working in concert, provide ... of information. The 3 major components of the brain are the cerebrum, cerebellum, and brain stem. The ...

  19. Brain surgery

    MedlinePlus

    Craniotomy; Surgery - brain; Neurosurgery; Craniectomy; Stereotactic craniotomy; Stereotactic brain biopsy; Endoscopic craniotomy ... cut depends on where the problem in the brain is located. The surgeon creates a hole in ...

  20. Brain Malformations

    MedlinePlus

    Most brain malformations begin long before a baby is born. Something damages the developing nervous system or causes it ... medicines, infections, or radiation during pregnancy interferes with brain development. Parts of the brain may be missing, ...

  1. ADS Development in Japan

    NASA Astrophysics Data System (ADS)

    Kikuchi, Kenji

    2010-06-01

    Accelerator driven nuclear transmutation system has been pursued to have a clue to the solution of high-level radioactive waste management. The concept consists of super conducting linac, sub-critical reactor and the beam window. Reference model is set up to 800MW thermal power by using 1.5GeV proton beams with considerations multi-factors such as core criticality. Materials damage is simulated by high-energy particle transport codes and so on. Recent achievement on irradiation materials experiment is stated and the differences are pointed out if core burn-up is considered or not. Heat balance in tank-type ADS indicates the temperature conditions of steam generator, the beam widow and cladding materials. Lead-bismuth eutectics demonstration has been conducted. Corrosion depth rate was shown by experiments.

  2. Supersymmetric warped AdS in extended topologically massive supergravity

    NASA Astrophysics Data System (ADS)

    Deger, N. S.; Kaya, A.; Samtleben, H.; Sezgin, E.

    2014-07-01

    We determine the most general form of off-shell N=(1,1) supergravity field configurations in three dimensions by requiring that at least one off-shell Killing spinor exists. We then impose the field equations of the topologically massive off-shell supergravity and find a class of solutions whose properties crucially depend on the norm of the auxiliary vector field. These are spacelike-squashed and timelike-stretched AdS3 for the spacelike and timelike norms, respectively. At the transition point where the norm vanishes, the solution is null warped AdS3. This occurs when the coefficient of the Lorentz-Chern-Simons term is related to the AdS radius by μℓ=2. We find that the spacelike-squashed AdS3 can be modded out by a suitable discrete subgroup of the isometry group, yielding an extremal black hole solution which avoids closed timelike curves.

  3. Fibrillar Amyloid-β Accumulation Triggers an Inflammatory Mechanism Leading to Hyperphosphorylation of the Carboxyl-Terminal End of Tau Polypeptide in the Hippocampal Formation of the 3×Tg-AD Transgenic Mouse.

    PubMed

    Ontiveros-Torres, Miguel Ángel; Labra-Barrios, María Luisa; Díaz-Cintra, Sofía; Aguilar-Vázquez, Azucena Ruth; Moreno-Campuzano, Samadhi; Flores-Rodríguez, Paola; Luna-Herrera, Claudia; Mena, Raúl; Perry, George; Florán-Garduño, Benjamín; Luna-Muñoz, José; Luna-Arias, Juan Pedro

    2016-03-22

    Alzheimer's disease (AD) is a degenerative and irreversible disorder whose progressiveness is dependent on age. It is histopathologically characterized by the massive accumulation of insoluble forms of tau and amyloid-β (Aβ) asneurofibrillary tangles and neuritic plaques, respectively. Many studies have documented that these two polypeptides suffer several posttranslational modifications employing postmortem tissue sections from brains of patients with AD. In order to elucidate the molecular mechanisms underlying the posttranslational modifications of key players in this disease, including Aβ and tau, several transgenic mouse models have been developed. One of these models is the 3×Tg-AD transgenic mouse, carrying three transgenes encoding APPSWE, S1M146V, and TauP301L proteins. To further characterize this transgenicmouse, we determined the accumulation of fibrillar Aβ as a function of age in relation to the hyperphosphorylation patterns of TauP301L at both its N- and C-terminus in the hippocampal formation by immunofluorescence and confocal microscopy. Moreover, we searched for the expression of activated protein kinases and mediators of inflammation by western blot of wholeprotein extracts from hippocampal tissue sections since 3 to 28 months as well. Our results indicate that the presence of fibrillar Aβ deposits correlates with a significant activation of astrocytes and microglia in subiculum and CA1 regions of hippocampus. Accordingly, we also observed a significant increase in the expression of TNF-α associated to neuritic plaques and glial cells. Importantly, there is an overexpression of the stress activated protein kinases SAPK/JNK and Cdk-5 in pyramidal neurons, which might phosphorylate several residues at the C-terminus of TauP301L. Therefore, the accumulation of Aβ oligomers results in an inflammatory environment that upregulates kinases involved in hyperphosphorylation of TauP301L polypeptide. PMID:27031470

  4. Brain trace elements and aging

    NASA Astrophysics Data System (ADS)

    Hebbrecht, Geert; Maenhaut, Willy; Reuck, Jacques De

    1999-04-01

    Degenerative mechanisms involved in the aging process of the brain are to a certain extent counteracted by repair mechanisms. In both degenerative and recovery processes, trace elements are involved. The present study focused on the role of two minor (i.e., K and Ca) and six trace elements (i.e., Mn, Fe, Cu, Zn, Se and Rb) in the aging process. The elements were determined by PIXE in cerebral cortex and white matter, basal ganglia, brainstem and cerebellar cortex of 18 postmortem human brains, from persons without a history of neurologic or psychiatric disease who deceased between the age of 7 and 79. This age range allowed us to study the relationship between elemental concentrations and age. The most prominent findings were a concentration decrease for K and Rb and a concentration increase for the elements Ca, Fe, Zn and Se. The study supports recent findings that Ca and Fe are involved in brain degenerative processes initiated by oxygen free radicals, whereas Zn and Se are involved in immunological reactions counteracting the aging process.

  5. Neuroimaging in repetitive brain trauma

    PubMed Central

    2014-01-01

    Sports-related concussions are one of the major causes of mild traumatic brain injury. Although most patients recover completely within days to weeks, those who experience repetitive brain trauma (RBT) may be at risk for developing a condition known as chronic traumatic encephalopathy (CTE). While this condition is most commonly observed in athletes who experience repetitive concussive and/or subconcussive blows to the head, such as boxers, football players, or hockey players, CTE may also affect soldiers on active duty. Currently, the only means by which to diagnose CTE is by the presence of phosphorylated tau aggregations post-mortem. Non-invasive neuroimaging, however, may allow early diagnosis as well as improve our understanding of the underlying pathophysiology of RBT. The purpose of this article is to review advanced neuroimaging methods used to investigate RBT, including diffusion tensor imaging, magnetic resonance spectroscopy, functional magnetic resonance imaging, susceptibility weighted imaging, and positron emission tomography. While there is a considerable literature using these methods in brain injury in general, the focus of this review is on RBT and those subject populations currently known to be susceptible to RBT, namely athletes and soldiers. Further, while direct detection of CTE in vivo has not yet been achieved, all of the methods described in this review provide insight into RBT and will likely lead to a better characterization (diagnosis), in vivo, of CTE than measures of self-report. PMID:25031630

  6. Postmortem CT is more accurate than clinical diagnosis for identifying the immediate cause of death in hospitalized patients: a prospective autopsy-based study.

    PubMed

    Inai, Kunihiro; Noriki, Sakon; Kinoshita, Kazuyuki; Sakai, Toyohiko; Kimura, Hirohiko; Nishijima, Akihiko; Iwasaki, Hiromichi; Naiki, Hironobu

    2016-07-01

    Despite 75 to 90 % physician accuracy in determining the underlying cause of death, precision of determination of the immediate cause of death is approximately 40 %. In contrast, two thirds of immediate causes of death in hospitalized patients are correctly diagnosed by postmortem computed tomography (CT). Postmortem CT might provide an alternative approach to verifying the immediate cause of death. To evaluate the effectiveness of postmortem CT as an alternative method to determine the immediate cause of death in hospitalized patients, an autopsy-based prospective study was performed. Of 563 deaths from September 2011 to August 2013, 50 consecutive cadavers undergoing hospital autopsies with consent for additional postmortem CT at the University of Fukui were enrolled. The accuracy of determination of the immediate cause of death by postmortem CT was evaluated in these patients. Diagnostic discrepancy was also compared between radiologists and attending physicians. The immediate cause of death was correctly diagnosed in 37 of 50 subjects using postmortem CT (74 %), concerning 29 cases of respiratory failure, 4 of hemorrhage, 3 of liver failure and 1 of septic shock. Six cases of organ failure involving 13 patients were not identified as the cause of death by postmortem CT. Regarding the immediate cause of death, accuracy of clinical diagnosis was significantly lower than that of postmortem CT (46 vs 74 %, P < 0.01). Postmortem CT may be more useful than clinical diagnosis for identifying the immediate cause of death in hospitalized patients not undergoing autopsy. PMID:27085336

  7. Role of extracellular matrix in development of skeletal muscle and postmortem aging of meat.

    PubMed

    Nishimura, Takanori

    2015-11-01

    The integrity of skeletal muscle is maintained by the intramuscular connective tissues (IMCTs) that are composed of extracellular matrix (ECM) molecules such as collagens, proteoglycans, and glycoproteins. The ECM plays an important role not only in providing biomechanical strength of the IMCT, but also in regulating muscle cell behavior. Some ECM molecules, such as decorin and laminin, modulate the activity of myostatin that regulates skeletal muscle mass. Furthermore, it has been shown that decorin activates Akt downstream of insulin-like growth factor-I receptor (IGF-IR) and enhances the differentiation of myogenic cells, suggesting that decorin acts as a signaling molecule to myogenic cells. With animal growth, the structural integrity of IMCT increases; collagen fibrils within the endomysium associate more closely with each other, and the collagen fibers in the perimysium become increasingly thick and their wavy pattern grows more regular. These changes increase the mechanical strength of IMCT, contributing to the toughening of meat. However, in highly marbled beef cattle like Wagyu, intramuscular fat deposits mainly in the perimysium between muscle fiber bundles during the fattening period. The development of adipose tissues appears to disorganize the structure of IMCT and contributes to the tenderness of Wagyu beef. The IMCT was considered to be rather immutable compared to myofibrils during postmortem aging of meat. However, several studies have shown that collagen networks in the IMCT are disintegrated and proteoglycan components are degraded during postmortem aging. These changes in ECM appear to reduce the mechanical strength of IMCT and contribute to the tenderness of uncooked meat or cooked meat at low temperature. Thus, the ECM plays a multifunctional role in skeletal muscle development and postmortem aging of meat. PMID:26141816

  8. Injury-related mortality in South Africa: a retrospective descriptive study of postmortem investigations

    PubMed Central

    Prinsloo, Megan; Pillay-van Wyk, Victoria; Gwebushe, Nomonde; Mathews, Shanaaz; Martin, Lorna J; Laubscher, Ria; Abrahams, Naeemah; Msemburi, William; Lombard, Carl; Bradshaw, Debbie

    2015-01-01

    Abstract Objective To investigate injury-related mortality in South Africa using a nationally representative sample and compare the results with previous estimates. Methods We conducted a retrospective descriptive study of medico-legal postmortem investigation data from mortuaries using a multistage random sample, stratified by urban and non-urban areas and mortuary size. We calculated age-specific and age-standardized mortality rates for external causes of death. Findings Postmortem reports revealed 52 493 injury-related deaths in 2009 (95% confidence interval, CI: 46 930–58 057). Almost half (25 499) were intentionally inflicted. Age-standardized mortality rates per 100 000 population were as follows: all injuries: 109.0 (95% CI: 97.1–121.0); homicide 38.4 (95% CI: 33.8–43.0; suicide 13.4 (95% CI: 11.6–15.2) and road-traffic injury 36.1 (95% CI: 30.9–41.3). Using postmortem reports, we found more than three times as many deaths from homicide and road-traffic injury than had been recorded by vital registration for this period. The homicide rate was similar to the estimate for South Africa from a global analysis, but road-traffic and suicide rates were almost fourfold higher. Conclusion This is the first nationally representative sample of injury-related mortality in South Africa. It provides more accurate estimates and cause-specific profiles that are not available from other sources. PMID:26229201

  9. Factors impacting the success of post-mortem sperm rescue in the rhinoceros.

    PubMed

    Roth, T L; Stoops, M A; Robeck, T R; O'Brien, J K

    2016-04-01

    The goal of this study was to identify factors that influenced the ability to successfully rescue sperm post-mortem from rhinoceroses maintained in North American zoos. Factors considered included procedural technicalities, individual rhinoceros characteristics and timing. Gross testicular pathology was noted in 17.4% of males (4/23) but did not impact sperm recovery except in one case of azoospermia (4.3%). Of the males in which sperm recovery was attempted (n=21), 62% yielded quality samples considered adequate for cryopreservation (≥ 30% motility with ≥ 2.0 forward progressive status). A high percentage of males (70.6%; 12/17) from which reproductive tissue was removed an d cooled ≤ 4 h after death yielded quality sperm samples, whereas only 25% (1/4) of males from which tissue was removed>4h after death yielded quality samples. Quality samples were recovered 1-51 h post-mortem from rhinoceroses 8 to 36 years old. Neither type of illness (prolonged or acute), or method of death (euthanasia or natural) affected the ability to harvest quality samples (P > 0.05). The Indian rhinoceros yielded significantly more sperm on average (40 × 10(9)) than the African black rhinoceros (3.6 × 10(9); P < 0.01) and the African white rhinoceros (3.2 × 10(9); P < 0.05). Across all species and samples assessed (n = 11), mean post-thaw sperm motility (41%), was only 15% less than pre-freeze motility (56%) and only decreased to 22% during the 6h post-thaw assessment period. Rhinoceros sperm rescue post-mortem is relatively successful across a wide range of variables, especially when tissues are removed and cooled promptly after death, and should be considered standard practice among zoos. PMID:26879096

  10. When gas analysis assists with postmortem imaging to diagnose causes of death.

    PubMed

    Varlet, V; Smith, F; Giuliani, N; Egger, C; Rinaldi, A; Dominguez, A; Chevallier, C; Bruguier, C; Augsburger, M; Mangin, P; Grabherr, S

    2015-06-01

    Postmortem imaging consists in the non-invasive examination of bodies using medical imaging techniques. However, gas volume quantification and the interpretation of the gas collection results from cadavers remain difficult. We used whole-body postmortem multi-detector computed tomography (MDCT) followed by a full autopsy or external examination to detect the gaseous volumes in bodies. Gases were sampled from cardiac cavities, and the sample compositions were analyzed by headspace gas chromatography-mass spectrometry/thermal conductivity detection (HS-GC-MS/TCD). Three categories were defined according to the presumed origin of the gas: alteration/putrefaction, high-magnitude vital gas embolism (e.g., from scuba diving accident) and gas embolism of lower magnitude (e.g., following a traumatic injury). Cadaveric alteration gas was diagnosed even if only one gas from among hydrogen, hydrogen sulfide or methane was detected. In alteration cases, the carbon dioxide/nitrogen ratio was often >0.2, except in the case of advanced alteration, when methane presence was the best indicator. In the gas embolism cases (vital or not), hydrogen, hydrogen sulfide and methane were absent. Moreover, with high-magnitude vital gas embolisms, carbon dioxide content was >20%, and the carbon dioxide/nitrogen ratio was >0.2. With gas embolisms of lower magnitude (gas presence consecutive to a traumatic injury), carbon dioxide content was <20% and the carbon dioxide/nitrogen ratio was often <0.2. We found that gas analysis provided useful assistance to the postmortem imaging diagnosis of causes of death. Based on the quantifications of gaseous cardiac samples, reliable indicators were determined to document causes of death. MDCT examination of the body must be performed as quickly as possible, as does gas sampling, to avoid generating any artifactual alteration gases. Because of cardiac gas composition analysis, it is possible to distinguish alteration gases and gas embolisms of different

  11. An accurate method for the determination of carboxyhemoglobin in postmortem blood using GC-TCD.

    PubMed

    Lewis, Russell J; Johnson, Robert D; Canfield, Dennis V

    2004-01-01

    During the investigation of aviation accidents, postmortem samples from accident victims are submitted to the FAA's Civil Aerospace Medical Institute for toxicological analysis. In order to determine if an accident victim was exposed to an in-flight/postcrash fire or faulty heating/exhaust system, the analysis of carbon monoxide (CO) is conducted. Although our laboratory predominantly uses a spectrophotometric method for the determination of carboxyhemoglobin (COHb), we consider it essential to confirm with a second technique based on a different analytical principle. Our laboratory encountered difficulties with many of our postmortem samples while employing a commonly used GC method. We believed these problems were due to elevated methemoglobin (MetHb) concentration in our specimens. MetHb does not bind CO; therefore, elevated MetHb levels will result in a loss of CO-binding capacity. Because most commonly employed GC methods determine %COHb from a ratio of unsaturated blood to CO-saturated blood, a loss of CO-binding capacity will result in an erroneously high %COHb value. Our laboratory has developed a new GC method for the determination of %COHb that incorporates sodium dithionite, which will reduce any MetHb present to Hb. Using blood controls ranging from 1% to 67% COHb, we found no statistically significant differences between %COHb results from our new GC method and our spectrophotometric method. To validate the new GC method, postmortem samples were analyzed with our existing spectrophotometric method, a GC method commonly used without reducing agent, and our new GC method with the addition of sodium dithionite. As expected, we saw errors up to and exceeding 50% when comparing the unreduced GC results with our spectrophotometric method. With our new GC procedure, the error was virtually eliminated. PMID:14987426

  12. Value Added in English Schools

    ERIC Educational Resources Information Center

    Ray, Andrew; McCormack, Tanya; Evans, Helen

    2009-01-01

    Value-added indicators are now a central part of school accountability in England, and value-added information is routinely used in school improvement at both the national and the local levels. This article describes the value-added models that are being used in the academic year 2007-8 by schools, parents, school inspectors, and other…

  13. Per aspirin ad astra...

    PubMed

    Hartung, Thomas

    2009-12-01

    Taking the 110th anniversary of marketing of aspirin as starting point, the almost scary toxicological profile of aspirin is contrasted with its actual use experience. The author concludes that we are lucky that, in 1899, there was no regulatory toxicology. Adding, for the purpose of this article, a fourth R to the Three Rs, i.e. Realism, three reality-checks are carried out. The first one comes to the conclusion that the tools of toxicology are hardly adequate for the challenges ahead. The second one concludes that, specifically, the implementation of the EU REACH system is not feasible with these tools, mainly with regard to throughput. The third one challenges the belief that classical alternative methods, i.e. replacing animal test-based tools one by one, is actually leading to a new toxicology - it appears to change only patches of the patchwork, but not to overcome any inherent limitations other than ethical ones. The perspective lies in the Toxicology for the 21st Century initiatives, which aim to create a new approach from the scratch, by an evidence-based toxicology and a global "Human Toxicology Programme". PMID:20105011

  14. Post-mortem re-cloning of a transgenic red fluorescent protein dog

    PubMed Central

    Hong, So Gun; Koo, Ok Jae; Oh, Hyun Ju; Park, Jung Eun; Kim, Minjung; Kim, Geon-A; Park, Eun Jung; Jang, Goo

    2011-01-01

    Recently, the world's first transgenic dogs were produced by somatic cell nuclear transfer. However, cellular senescence is a major limiting factor for producing more advanced transgenic dogs. To overcome this obstacle, we rejuvenated transgenic cells using a re-cloning technique. Fibroblasts from post-mortem red fluorescent protein (RFP) dog were reconstructed with in vivo matured oocytes and transferred into 10 surrogate dogs. One puppy was produced and confirmed as a re-cloned dog. Although the puppy was lost during birth, we successfully established a rejuvenated fibroblast cell line from this animal. The cell line was found to stably express RFP and is ready for additional genetic modification. PMID:22122908

  15. Effect of post-mortem handling conditions on the quality of spent hen meat curry.

    PubMed

    Mendiratta, S K; Sharma, B D; Majhi, M; Kumar, R R

    2012-04-01

    Study was performed to determine the effect of post-mortem handling conditions on the physico-chemical and sensory attributes of spent hen meat curry. Breast cuts of spent hens were subjected to different postmortem handling conditions before cooking viz; made into small cuts and cooked within 1-2 h of slaughter (condition 1), made into small cuts and cooked after 4-5 h of slaughter (condition 2), made into small cuts immediately after slaughter, stored at 4 ± 1 °C for 12 h and then cooked (condition 3), stored at 4 ± 1 °C for 12 h, made into small cuts and cooked (condition 4). The pH of meat just before cooking due to different stages of rigor development under various conditions differed accordingly. Observed differences in temperature of meat just before cooking were because of different postmortem handling condition variations viz:1,2,3,&4. The associated post mortem changes under different postmortem handling conditions before cooking led to significant variation in Water holding capacity, Water Soluble Protein, Salt Soluble Protein, cooking yield, moisture percentage before cooking and after cooking and also WB shear force value. In general, sensory scores were higher for conditions 4 and 1 as compared to conditions 2 and 3. Results revealed that quality attributes of spent hen meat curry can be improved by following proper post-slaughter handling and processing conditions. To get meat curry of good sensory quality, meat should be cooked preferably within 1-2 h of slaughter or after 10-12 h of storage of intact carcass at 4 ± 1 °C. Cuts should be made just before cooking but cooking after 4-5 h of slaughter should be avoided. PMID:23572849

  16. A new method for determination of postmortem left ventricular volumes: clinico-pathologic correlations.

    PubMed

    Wissler, R W; Lichtig, C; Hughes, R; Al-Sadir, J; Glagov, S

    1975-05-01

    A description is presented of a new and simple procedure for ventricular volume determination by means of pressure fixation of the heart and preparation of plastic molds of the ventricles which can be used to displace water in a graduated cylinder to determine the volume of the mold. Correlations between postmortem ventricular volume as measured by this method and antemortem stroke volume or clinical cardiac status indicate that a large left ventricular volume is often correlated with a low cardiac output and cardiogenic shock. PMID:1119371

  17. Comparison of Hybrid-III and postmortem human surrogate response to simulated underbody blast loading.

    PubMed

    Bailey, Ann Marie; Christopher, John J; Salzar, Robert S; Brozoski, Frederick

    2015-05-01

    Response of the human body to high-rate vertical loading, such as military vehicle underbody blast (UBB), is not well understood because of the chaotic nature of such events. The purpose of this research was to compare the response of postmortem human surrogates (PMHS) and the Hybrid-III anthropomorphic test device (ATD) to simulated UBB loading ranging from 100 to 860 g seat and floor acceleration. Data from 13 whole body PMHS tests were used to create response corridors for vertical loading conditions for the pelvis, T1, head, femur, and tibia; these responses were compared to Hybrid-III responses under matched loading conditions. PMID:25751733

  18. Diagnostic accuracy of double-contrast arthrotomography of the temporomandibular joint: correlation with postmortem morphology

    SciTech Connect

    Westesson, P.L.; Rohlin, M.

    1984-09-01

    The diagnostic accuracy of double-contrast arthrotomography in the evaluation of internal derangement of the temporomandibular joint is unknown. Therefore, findings from double-contrast arthrotomograms of 48 temporomandibular joint autopsy specimens were correlated with postmortem morphology seen from dissections or cryosections. Arthrotomographic diagnosis was confirmed in 41 joints, signifying a diagnostic accuracy of 85%. Misinterpretations were made in seven joints. False-positive reports due to observation errors can be avoided with improved knowledge of the joint anatomy as well as with increased experience in the technique. False-negative examinations were due to limitation of the tomographic reproduction of the lateral part of the joint.

  19. Perinatal and paediatric post-mortem magnetic resonance imaging (PMMR): sequences and technique.

    PubMed

    Norman, Wendy; Jawad, Noorulhuda; Jones, Rod; Taylor, Andrew M; Arthurs, Owen J

    2016-06-01

    As post-mortem MRI (PMMR) becomes more widely used for investigation following perinatal and paediatric deaths, the best possible images should be acquired. In this article, we review the most widely used published PMMR sequences, together with outlining our acquisition protocol and sequence parameters for foetal, perinatal and paediatric PMMR. We give examples of both normal and abnormal appearances, so that the reader can understand the logic behind each acquisition step before interpretation, as a useful day-to-day reference guide to performing PMMR. PMID:26916282

  20. Adult post-mortem imaging in traumatic and cardiorespiratory death and its relation to clinical radiological imaging

    PubMed Central

    Adlam, D; Robinson, C; Pakkal, M; Rutty, G N

    2014-01-01

    The use of post-mortem imaging is expanding throughout the world with increasing use of advanced imaging techniques, such as contrast-enhanced CT and MRI. The questions asked of post-mortem imaging are complex and can be very different, for example for natural sudden death investigation will focus on the cause, whereas for trauma the cause of death is often clear, but injury patterns may be very revealing in investigating the background to the incident. Post-mortem imaging is different to clinical imaging regarding both the appearance of pathology and the information required, but there is much to learn from many years of clinical research in the use of these techniques. Furthermore, it is possible that post-mortem imaging research could be used not only for investigating the cause of death but also as a model to conduct clinically relevant research. This article reviews challenges to the development of post-mortem imaging for trauma, identification and cardiorespiratory death, and how they may be influenced by current clinical thinking and practice. PMID:24338941

  1. The social life of the dead: The role of post-mortem examinations in medical student socialisation.

    PubMed

    Goodwin, Dawn; Machin, Laura; Taylor, Adam

    2016-07-01

    Dissection has held a privileged position in medical education although the professional values it inculcates have been subject to intense debate. Claims vary from it generating a dehumanising level of emotional detachment, to promotion of rational and dispassionate decision-making, even to being a positive vehicle for ethical education. Social scientists have positioned dissection as a critical experience in the emotional socialisation of medical students. However, curricular revision has provoked debate about the style and quantity of anatomy teaching thus threatening this 'rite of passage' of medical students. Consequently, some UK medical schools do not employ dissection at all. In its place, observation of post-mortem examinations - a long established, if underutilised, practice - has re-emerged in an attempt to recoup aspects of anatomical knowledge that are arguably lost when dissection is omitted. Bodies for post-mortem examinations and bodies for dissection, however, have striking differences, meaning that post-mortem examinations and dissection cannot be considered comparable opportunities to learn anatomy. In this article, we explore the distinctions between dissection and post-mortem examinations. In particular, we focus on the absence of a discourse of consent, concerns about bodily integrity, how the body's shifting ontology, between object and person, disrupts students' attempts to distance themselves, and how the observation of post-mortem examinations features in the emotional socialisation of medical students. PMID:27261534

  2. Development and validation of a dynamic range-extended LC-MS/MS multi-analyte method for 11 different postmortem matrices for redistribution studies applying solvent calibration and additional (13)C isotope monitoring.

    PubMed

    Staeheli, Sandra N; Poetzsch, Michael; Kraemer, Thomas; Steuer, Andrea E

    2015-11-01

    Postmortem redistribution (PMR) is one of numerous problems in postmortem toxicology making correct interpretation of measured drug concentrations difficult or even impossible. Time-dependent PMR in peripheral blood and especially in tissue samples is still under-explored. For further investigation, an easy applicable method for the simultaneous quantitation of over 80 forensically relevant compounds in 11 different postmortem matrices should be developed and validated overcoming the challenges of high inter-matrix and intra-matrix concentration variances. Biopsy samples (20 mg) or body fluids (20 μL) were spiked with an analyte mix and deuterated internal standards, extracted by liquid-liquid extraction, and analyzed by liquid chromatography tandem mass spectrometry (LC-MS/MS). For highest applicability, an easy solvent calibration was used. Furthermore, time-consuming dilution of high concentration samples showing detector saturation was circumvented by two overlapping calibration curves using (12)C isotope monitoring for low concentrations and (13)C isotopes for high concentration, respectively. The method was validated according to international guidelines with modifications. Matrix effects and extraction efficiency were strongly matrix and analyte dependent. In general, brain and adipose tissue produced the highest matrix effects, whereas cerebrospinal fluid showed the least matrix effects. Accuracy and precision results were rather matrix independent with some exceptions. Despite using an external solvent calibration, the accuracy requirements were fulfilled for 66 to 81 % of the 83 analytes. Depending on the matrix, 75-93 % of the analytes showed intra-day precisions at <20 %. (12)C and (13)C calibrations gave comparable results and proved to be a useful tool in expanding the dynamic range. PMID:26396081

  3. Multiplex analyte assays to characterize different dementias: brain inflammatory cytokines in poststroke and other dementias.

    PubMed

    Chen, Aiqing; Oakley, Arthur E; Monteiro, Maria; Tuomela, Katri; Allan, Louise M; Mukaetova-Ladinska, Elizabeta B; O'Brien, John T; Kalaria, Raj N

    2016-02-01

    Both the inflammatory potential and cognitive function decline during aging. The association between the repertoire of inflammatory biomarkers and cognitive decline is unclear. Inflammatory cytokines have been reported to be increased, decreased, or unchanged in the cerebrospinal fluid and sera of subjects with dementia. We assessed 112 postmortem brains from subjects diagnosed with poststroke dementia (PSD), vascular dementia, mixed dementia, and Alzheimer's disease (AD), comparing those to poststroke nondemented (PSND) subjects and age-matched controls. We analyzed 5 brain regions including the gray and white matter from the frontal and temporal lobes for a panel of cytokine and/or chemokine analytes using multiplex-array assays. Of the 37 analytes, 14 were under or near the detection limits, 7 were close to the lowest detection level, and 16 cytokines were within the linear range of the assay. We observed widely variable concentrations of C-reactive protein (CRP) and serum amyloid A at the high end (1-150 ng/mg protein), whereas several of the interleukins (IL, interferon-gamma and tumor necrosis factor) at the low end (1-10 pg/mg). There were also regional variations; most notable being high concentrations of some cytokines (e.g., CRP and angiogenesis panel) in the frontal white matter. Overall, we found decreased concentrations of several cytokines, including IL-1 beta (p = 0.000), IL-6 (p = 0.000), IL-7 (p = 0.000), IL-8 (p = 0.000), IL-16 (p = 0.001), interferon-inducible protein-10 (0.044), serum amyloid A (p = 0.011), and a trend in IL-1 alpha (p = 0.084) across all dementia groups compared to nondemented controls. IL-6 and IL-8 were significantly lower in dementia subjects than in nondemented subjects in every region. In particular, lower levels of IL-6 and IL-8 were notable in the PSD compared to PSND subjects. Because these 2 stroke groups had comparable degree of vascular pathology, the lower production of IL-6 and IL-8 in PSD reaffirms a

  4. Multiplex analyte assays to characterize different dementias: brain inflammatory cytokines in poststroke and other dementias

    PubMed Central

    Chen, Aiqing; Oakley, Arthur E.; Monteiro, Maria; Tuomela, Katri; Allan, Louise M.; Mukaetova-Ladinska, Elizabeta B.; O'Brien, John T.; Kalaria, Raj N.

    2016-01-01

    Both the inflammatory potential and cognitive function decline during aging. The association between the repertoire of inflammatory biomarkers and cognitive decline is unclear. Inflammatory cytokines have been reported to be increased, decreased, or unchanged in the cerebrospinal fluid and sera of subjects with dementia. We assessed 112 postmortem brains from subjects diagnosed with poststroke dementia (PSD), vascular dementia, mixed dementia, and Alzheimer's disease (AD), comparing those to poststroke nondemented (PSND) subjects and age-matched controls. We analyzed 5 brain regions including the gray and white matter from the frontal and temporal lobes for a panel of cytokine and/or chemokine analytes using multiplex-array assays. Of the 37 analytes, 14 were under or near the detection limits, 7 were close to the lowest detection level, and 16 cytokines were within the linear range of the assay. We observed widely variable concentrations of C-reactive protein (CRP) and serum amyloid A at the high end (1–150 ng/mg protein), whereas several of the interleukins (IL, interferon-gamma and tumor necrosis factor) at the low end (1–10 pg/mg). There were also regional variations; most notable being high concentrations of some cytokines (e.g., CRP and angiogenesis panel) in the frontal white matter. Overall, we found decreased concentrations of several cytokines, including IL-1 beta (p = 0.000), IL-6 (p = 0.000), IL-7 (p = 0.000), IL-8 (p = 0.000), IL-16 (p = 0.001), interferon-inducible protein–10 (0.044), serum amyloid A (p = 0.011), and a trend in IL-1 alpha (p = 0.084) across all dementia groups compared to nondemented controls. IL-6 and IL-8 were significantly lower in dementia subjects than in nondemented subjects in every region. In particular, lower levels of IL-6 and IL-8 were notable in the PSD compared to PSND subjects. Because these 2 stroke groups had comparable degree of vascular pathology, the lower production of IL-6 and IL-8 in PSD reaffirms a

  5. Supergravity at the boundary of AdS supergravity

    NASA Astrophysics Data System (ADS)

    Amsel, Aaron J.; Compère, Geoffrey

    2009-04-01

    We give a general analysis of AdS boundary conditions for spin-3/2 Rarita-Schwinger fields and investigate boundary conditions preserving supersymmetry for a graviton multiplet in AdS4. Linear Rarita-Schwinger fields in AdSd are shown to admit mixed Dirichlet-Neumann boundary conditions when their mass is in the range 0≤|m|<1/2lAdS. We also demonstrate that mixed boundary conditions are allowed for larger masses when the inner product is “renormalized” accordingly with the action. We then use the results obtained for |m|=1/lAdS to explore supersymmetric boundary conditions for N=1 AdS4 supergravity in which the metric and Rarita-Schwinger fields are fluctuating at the boundary. We classify boundary conditions that preserve boundary supersymmetry or superconformal symmetry. Under the AdS/CFT dictionary, Neumann boundary conditions in d=4 supergravity correspond to gauging the superconformal group of the three-dimensional CFT describing M2-branes, while N=1 supersymmetric mixed boundary conditions couple the CFT to N=1 superconformal topologically massive gravity.

  6. Visualization of monoamine oxidase in human brain

    SciTech Connect

    Fowler, J.S.; Volkow, N.D.; Wang, G.J.; Pappas, N.; Shea, C.; MacGregor, R.R.; Logan, J.

    1996-12-31

    Monoamine oxidase is a flavin enzyme which exists in two subtypes, MAO A and MAO B. In human brain MAO B predominates and is largely compartmentalized in cell bodies of serotonergic neurons and glia. Regional distribution of MAO B was determined by positron computed tomography with volunteers after the administration of deuterium substituted [11C]L-deprenyl. The basal ganglia and thalamus exhibited the greatest concentrations of MAO B with intermediate levels in the frontal cortex and cingulate gyrus while lowest levels were observed in the parietal and temporal cortices and cerebellum. We observed that brain MAO B increases with are in health normal subjects, however the increases were generally smaller than those revealed with post-mortem studies.

  7. Sports-related brain injuries: connecting pathology to diagnosis.

    PubMed

    Pan, James; Connolly, Ian D; Dangelmajer, Sean; Kintzing, James; Ho, Allen L; Grant, Gerald

    2016-04-01

    Brain injuries are becoming increasingly common in athletes and represent an important diagnostic challenge. Early detection and management of brain injuries in sports are of utmost importance in preventing chronic neurological and psychiatric decline. These types of injuries incurred during sports are referred to as mild traumatic brain injuries, which represent a heterogeneous spectrum of disease. The most dramatic manifestation of chronic mild traumatic brain injuries is termed chronic traumatic encephalopathy, which is associated with profound neuropsychiatric deficits. Because chronic traumatic encephalopathy can only be diagnosed by postmortem examination, new diagnostic methodologies are needed for early detection and amelioration of disease burden. This review examines the pathology driving changes in athletes participating in high-impact sports and how this understanding can lead to innovations in neuroimaging and biomarker discovery. PMID:27032917

  8. In vivo studies of brain development by magnetic resonance techniques.

    PubMed

    Inder, T E; Huppi, P S

    2000-01-01

    Understanding of the morphological development of the human brain has largely come from neuropathological studies obtained postmortem. Magnetic resonance (MR) techniques have recently allowed the provision of detailed structural, metabolic, and functional information in vivo on the human brain. These techniques have been utilized in studies from premature infants to adults and have provided invaluable data on the sequence of normal human brain development. This article will focus on MR techniques including conventional structural MR imaging techniques, quantitative morphometric MR techniques, diffusion weighted MR techniques, and MR spectroscopy. In order to understand the potential applications and limitations of MR techniques, relevant physical and biological principles for each of the MR techniques are first reviewed. This is followed by a review of the understanding of the sequence of normal brain development utilizing these techniques. MRDD Research Reviews 6:59-67, 2000. PMID:10899798

  9. Rho Kinase Pathway Alterations in the Brain and Leukocytes in Huntington's Disease.

    PubMed

    Narayanan, K Lakshmi; Chopra, Vanita; Rosas, H Diana; Malarick, Keith; Hersch, Steven

    2016-05-01

    Huntington's disease (HD) is a fatal neurodegenerative disease caused by an expanded polyglutamine tract in the huntingtin gene. Therapeutic approaches targeting mutant huntingtin (mtHtt) or its downstream toxic consequences are under development, including Rho kinase pathway inhibition. We investigated the messenger RNA (mRNA) expression of Rho kinase pathway genes, including RhoA (Ras homolog family member A), ROCK1 (Rho-associated kinase1), PRK2 (protein kinase C-related protein kinase 2), Profilin1, cofilin1, MYPT1 (myosin phosphatase target subunit 1), and LIMK1 (LIM domain kinase 1) in HD human blood leukocytes, postmortem brain, and in R6/2 HD mouse brain tissue using qPCR. RhoA, ROCK1, PRK2, Profilin1, cofilin1, and MYPT1 were significantly increased in HD blood compared to controls. In frontal cortex of HD postmortem brain tissue, the expression of RhoA, ROCK1, PRK2, Profilin1, and MYPT1 were also significantly increased. In the brain from 4-week-old R6/2 mice, the expression of Rock1, Prk2, Cofilin1, and MYPT1 was significantly increased while RhoA, Rock1, Profilin1, Cofilin1, and Mypt1 were increased and Limk1 mRNA decreased in 13-week-old R6/2 mice. Western blot analysis using human postmortem tissues for ROCK1 and Profilin1 demonstrated significantly increased protein levels, which correlated with the mRNA increases. Collectively, we have shown the panel of Rho kinase pathway genes to be highly altered in human HD blood, postmortem brain tissue, and in R6/2 mice. These studies confirm that HD upregulates the Rho kinase pathway and identifies mRNAs that could serve as peripheral markers in HD patients and translational markers in HD mouse models. PMID:25941073

  10. Asymptotically AdS spacetimes with a timelike Kasner singularity

    NASA Astrophysics Data System (ADS)

    Ren, Jie

    2016-07-01

    Exact solutions to Einstein's equations for holographic models are presented and studied. The IR geometry has a timelike cousin of the Kasner singularity, which is the less generic case of the BKL (Belinski-Khalatnikov-Lifshitz) singularity, and the UV is asymptotically AdS. This solution describes a holographic RG flow between them. The solution's appearance is an interpolation between the planar AdS black hole and the AdS soliton. The causality constraint is always satisfied. The entanglement entropy and Wilson loops are discussed. The boundary condition for the current-current correlation function and the Laplacian in the IR is examined. There is no infalling wave in the IR, but instead, there is a normalizable solution in the IR. In a special case, a hyperscaling-violating geometry is obtained after a dimensional reduction.

  11. All AdS7 solutions of type II supergravity

    NASA Astrophysics Data System (ADS)

    Apruzzi, Fabio; Fazzi, Marco; Rosa, Dario; Tomasiello, Alessandro

    2014-04-01

    In M-theory, the only AdS7 supersymmetric solutions are AdS7 × S 4 and its orbifolds. In this paper, we find and classify new supersymmetric solutions of the type AdS7 × M 3 in type II supergravity. While in IIB none exist, in IIA with Romans mass (which does not lift to M-theory) there are many new ones. We use a pure spinor approach reminiscent of generalized complex geometry. Without the need for any Ansatz, the system determines uniquely the form of the metric and fluxes, up to solving a system of ODEs. Namely, the metric on M 3 is that of an S 2 fibered over an interval; this is consistent with the Sp(1) R-symmetry of the holographically dual (1,0) theory. By including D8 brane sources, one can numerically obtain regular solutions, where topologically M 3 ≅ S 3.

  12. Worldsheet scattering in AdS3/CFT2

    NASA Astrophysics Data System (ADS)

    Sundin, Per; Wulff, Linus

    2013-07-01

    We confront the recently proposed exact S-matrices for AdS 3/ CFT 2 with direct worldsheet calculations. Utilizing the BMN and Near Flat Space (NFS) expansions for strings on AdS 3 × S 3 × S 3 × S 1 and AdS 3 × S 3 × T 4 we compute both tree-level and one-loop scattering amplitudes. Up to some minor issues we find nice agreement in the tree-level sector. At the one-loop level however we find that certain non-zero tree-level processes, which are not visible in the exact solution, contribute, via the optical theorem, and give an apparent mismatch for certain amplitudes. Furthermore we find that a proposed one-loop modification of the dressing phase correctly reproduces the worldsheet calculation while the standard Hernandez-Lopez phase does not. We also compute several massless to massless processes.

  13. Detailed ultraviolet asymptotics for AdS scalar field perturbations

    NASA Astrophysics Data System (ADS)

    Evnin, Oleg; Jai-akson, Puttarak

    2016-04-01

    We present a range of methods suitable for accurate evaluation of the leading asymptotics for integrals of products of Jacobi polynomials in limits when the degrees of some or all polynomials inside the integral become large. The structures in question have recently emerged in the context of effective descriptions of small amplitude perturbations in anti-de Sitter (AdS) spacetime. The limit of high degree polynomials corresponds in this situation to effective interactions involving extreme short-wavelength modes, whose dynamics is crucial for the turbulent instabilities that determine the ultimate fate of small AdS perturbations. We explicitly apply the relevant asymptotic techniques to the case of a self-interacting probe scalar field in AdS and extract a detailed form of the leading large degree behavior, including closed form analytic expressions for the numerical coefficients appearing in the asymptotics.

  14. New massive gravity and AdS(4) counterterms.

    PubMed

    Jatkar, Dileep P; Sinha, Aninda

    2011-04-29

    We show that the recently proposed Dirac-Born-Infeld extension of new massive gravity emerges naturally as a counterterm in four-dimensional anti-de Sitter space (AdS(4)). The resulting on-shell Euclidean action is independent of the cutoff at zero temperature. We also find that the same choice of counterterm gives the usual area law for the AdS(4) Schwarzschild black hole entropy in a cutoff-independent manner. The parameter values of the resulting counterterm action correspond to a c=0 theory in the context of the duality between AdS(3) gravity and two-dimensional conformal field theory. We rewrite this theory in terms of the gauge field that is used to recast 3D gravity as a Chern-Simons theory. PMID:21635026

  15. Calpain proteolysis of alpha II-spectrin in the normal adult human brain.

    PubMed

    Huh, G Y; Glantz, S B; Je, S; Morrow, J S; Kim, J H

    2001-12-01

    The proteolysis of alphaII-spectrin by calpain may be physiologically involved with synaptic remodeling, long-term potentiation, and memory formation. Calpain activation may also mediate neuronal apoptosis, responses to hypoxic insult, and excitotoxic injury. Surprisingly little is known of the activity of these calpain-mediated processes in the adult human brain. Using an antibody that specifically recognizes calpain-cleaved alphaII-spectrin, we have mapped the topographic distribution of the major alphaII-spectrin break-down product (alphaII-bdp1) in six adult brains examined post-mortem. All brains were from patients without evident neurological disease. Focally positive alphaII-bdp1 was consistently detected in the neuropil of the cortical gray matter, in occasional pyramidal neurons, and in rare reactive astrocytes in the cerebral cortex and hippocampus. Cerebellar Purkinje cells were more frequently, and more intensely, immunopositive. In all fields, staining was most intense in the soma and dendrites of neurons. There was no correlation of the frequency of positive cells with the postmortem interval or clinical condition. While these findings do not rigorously exclude contributions from postmortem calpain activation, they do suggest that a low-level of calpain processing of alphaII-spectrin is likely to be a constitutive process in the adult human brain. PMID:11720774

  16. Magnetic resonance imaging in dementia. A study of brain white matter changes.

    PubMed

    Bronge, Lena

    2002-07-01

    Non-specific white matter changes (WMC) in the brain are common findings in the elderly population. Although they are frequently seen in non-demented persons, WMC seem to be more common in demented patients. The significance of these changes, as well as their pathophysiological background, is incompletely understood. The aim of this thesis was to study different aspects of WMC using MR imaging (MRI) and to investigate the clinical significance of such changes in subjects with mild cognitive impairment or dementia. In study I post-mortem MRI of the brain was compared to corresponding neuropathology slices. WMC were quantified and found to be more extensive on neuropathology. The areas that appeared normal on MRI but not on histopathology represented only minor changes with increased distance between the myelinated fibres but with preserved axonal network and glial cell density. Study II evaluated the blood-brain barrier (BBB) integrity to investigate if an increased permeability could be shown in WMC. A contrast-enhanced MRI technique was used to detect small degrees of enhancement. No general increase in BBB could be detected in the WMC areas. In study III the relation between WMC and apolipoprotein E (APOE) genotype was explored in patients with Alzheimer's disease (AD). Results showed that AD patients, who were homozygous for the APOE epsilon 4 allele had more WMC than patients with other genotypes. This was most significant for changes in the deep white matter. Results also indicated that in AD patients carrying the epsilon 4 allele, WMC are not age-related phenomena, but might be related to the aetiology of the disease. Study IV aimed to investigate if WMC in a specific brain region affect cognitive functions related to that area. Periventricular WMC in the left frontal lobe predicted a decrease in initial word fluency, a test though to reflect left frontal lobe functioning. This indicates that WMC might have specific effects in different brain regions. In

  17. Experimental taphonomy: post-mortem microstructural modifications in Sus scrofa domesticus bone.

    PubMed

    Kontopoulos, Ioannis; Nystrom, Pia; White, Lorraine

    2016-09-01

    Bone is a highly specialised form of hard and rigid connective tissue whose histological structure undergoes post-mortem modifications. In taphonomic research, histological examination of bone thin sections is used to investigate these post-mortem microstructural changes in skeletal tissues. In this study, diagenetic modifications in pig skeletal remains (Sus scrofa domesticus) which were exposed to different taphonomic conditions as part of a long-term, real-time experiment were examined under light microscope (i.e. plain and cross polarized light). This experiment demonstrated that macroscopic appearance and microscopic preservation of bone may significantly differ. Early microbial attack was identified as enlarged osteocyte lacunae that later coalesce to constitute larger foci. Additionally, microscopic preservation of different skeletal elements varied intra-individually, while within bone differential preservation (i.e. proximal versus distal ends) was also observed. However, no specific patterns of early histological attack (e.g. endosteal and periosteal destruction) and no clear relationship between histological preservation and proximity to the abdominal area were detected. Lastly, the presence and composition of protective textiles had a clear effect on bone preservation. This research project, therefore, provided important evidence for the better understanding of the diagenetic processes that occur within bones whilst buried or exposed on the ground surface. PMID:27368073

  18. Protein expression and oxygen consumption rate of early postmortem mitochondria relate to meat tenderness.

    PubMed

    Grabež, V; Kathri, M; Phung, V; Moe, K M; Slinde, E; Skaugen, M; Saarem, K; Egelandsdal, B

    2015-04-01

    Oxygen consumption rate (OCR) of muscle fibers from bovine semimembranosus muscle of 41 animals was investigated 3 to 4 h and 3 wk postmortem. Significant relations (P < 0.05) were found between OCR measurements and Warner-Bratzler shear force measurement. Muscles with high mitochondrial OCR after 3 to 4 h and low nonmitochondrial oxygen consumption gave more tender meat. Tender (22.92 ± 2.2 N/cm2) and tough (72.98 ± 7.2 N/cm2) meat samples (4 samples each), separated based on their OCR measurements, were selected for proteomic studies using mitochondria isolated approximately 2.5 h postmortem. Twenty-six differently expressed proteins (P < 0.05) were identified in tender meat and 19 in tough meat. In tender meat, the more prevalent antioxidant and chaperon enzymes may reduce reactive oxygen species and prolong oxygen removal by the electron transport system (ETS). Glycolytic, Krebs cycle, and ETS enzymes were also more abundant in tender meat PMID:26020220

  19. Field Documentation of Unusual Post-Mortem Arthropod Activity on Human Remains.

    PubMed

    Pechal, Jennifer L; Benbow, M Eric; Tomberlin, Jeffery K; Crippen, Tawni L; Tarone, Aaron M; Singh, Baneshwar; Lenhart, Paul A

    2015-01-01

    During a forensic investigation, the presence of physical marks on human remains can influence the interpretation of events related to the death of an individual. Some tissue injury on human remains can be misinterpreted as ante- or peri-mortem wounds by an investigator when in reality the markings resulted from post-mortem arthropod activity. Unusual entomological data were collected during a study examining the decomposition of a set of human remains in San Marcos, Texas. An adult female Pediodectes haldemani (Girard) (Orthoptera: Tettigoniidae) and an Armadillidium cf. vulgare (Isopoda: Armadilidiidae) were documented feeding on the remains. Both arthropods produced physical marks or artifacts on the remains that could be misinterpreted as attack, abuse, neglect, or torture. Additionally, red imported fire ants, Solenopsis invicta Buren (Hymenoptera: Formicidae), were observed constructing structures in the mark produced by the P. haldemani feeding. These observations provide insight into the potential of post-mortem arthropod damage to human remains, which previously had not been described for these taxa, and therefore, physical artifacts on any remains found in similar circumstances may result from arthropod activity and not ante- or peri-mortem wounds. PMID:26336287

  20. The assessment of lens opacity postmortem and its implication in forensics.

    PubMed

    Stemberga, Valter; Petaros, Anja; Kovacevic, Damir; Coklo, Miran; Simicevic, Neven; Bosnar, Alan

    2013-11-01

    Visual impairment, mostly due to cataracts, has been demonstrated to be an important factor associated with traffic accidents. Although vision screening is standard procedure during licensing in order to prevent motor vehicle accidents, an eye exam is not typically administered after an accident has already occurred. Postmortem assessment of lens opacity in victims of car accidents would provide helpful information for attesting to the liability of the parties in specific accidents, determining the circumstances of the accident, and developing preventive measures for both drivers and pedestrians alike. In this paper, we explore the use of different methods and their limitations for assessing lens opacity postmortem. We discuss the possible use and benefits of a simple, but as-yet untested method: retrobulbar translucency. The method would be based on the recording of shadows formed by opaque regions of the lens while the eye is illuminated from the back with a rigid source of light. The efficacy and objectivity of the method, its reproducibility, and the inter- and intra-observer error should be tested before implementing such a technique to be regularly used to determine lens opacity in cadavers. PMID:24237839

  1. Distinguishing between perimortem and postmortem fractures: are osteons of any help?

    PubMed

    Pechníková, Markéta; Porta, Davide; Cattaneo, Cristina

    2011-07-01

    The distinction between perimortem and postmortem fractures in forensic anthropology is still a frequently unsolved issue. In the present study, we try to verify if there are differences in the pattern of osteon fracturing between fresh and dry bone which could be used for such a diagnosis. Fresh and dry long bones were fractured by a hammer at the mid-shaft perpendicularly to the long axis of the bone and the fracture margins examined under a light microscope as undecalcified sections. Examination of 982 osteons (505 fresh, 477 dry) showed that twice as often the fracture line crosses the osteons as opposed to travelling around them, independently of whether the bone is fresh or dry. Statistical analysis confirmed that there was no significant difference between fresh and dry bone. This seems to imply that osteon fracture pattern cannot help in the diagnosis of perimortem versus postmortem bone fractures. Further research however must be performed concerning fast and slow energy dispersal which may have an influence on the type of fracture inflicted. PMID:21487677

  2. Clinical signs, treatment, and postmortem lesions in dairy goats with enterotoxemia: 13 cases (1979-1982).

    PubMed

    Blackwell, T E; Butler, D G

    1992-01-15

    Enterotoxemia attributable to Clostridium perfringens type D in goats is difficult to diagnose because of a lack of specific clinical signs or postmortem lesions, on which to base the diagnosis. This report describes the clinical signs, postmortem lesions, and clinical responses to treatment and vaccination in 4 goat herds, in which a diagnosis of enterotoxemia was confirmed. Four clinical cases had the diagnosis confirmed on the basis of signs of diarrhea or sudden death and the isolation of C perfringens and epsilon toxin from the feces at the time of admission. The 10 necropsy cases were diagnosed on the basis of the isolation of C perfringens (not typed) or epsilon toxin from the intestinal contents of goats that died with clinical signs compatible with enterotoxemia and without lesions associated with a second serious disease. Enterocolitis was the most consistent lesion reported at necropsy in the 10 goats with enterotoxemia. Ovine enterotoxemia vaccines were of limited value in preventing enterotoxemia. These observations imply that naturally induced enterotoxemia in goats involves a different pathophysiologic mechanism than that associated with enterotoxemia in sheep. PMID:1559880

  3. Measurement of the pH value in pork meat early postmortem by Raman spectroscopy

    NASA Astrophysics Data System (ADS)

    Scheier, R.; Schmidt, H.

    2013-05-01

    The pH of a muscle is an accepted parameter to identify normal and deviating meat qualities. In this work, Raman spectroscopy is shown to be suitable for the non-invasive measurement of the early postmortem pH of meat. Raman spectra of ten pork semimembranosus muscles were recorded with a portable handheld device 0.5-24 h postmortem. The spectra were correlated with pH and lactate kinetics measured in parallel. Seven of the muscles were normal, two exhibited accelerated glycolysis and one showed absence of acidification. The pH decline with time could be calculated from the Raman spectra with the Henderson-Hasselbalch equation using only two signals of phosphate vibrations at 980 and 1,080 cm-1 with a close correlation for each muscle, but larger variations between animals. More robust and better correlations for all muscles were obtained with a linear model based on 11 signals from lactate, lactic acid, phosphate, a carbonyl band and nucleotides resulting in R 2 = 0.78 and RMSECV = 0.2 or a partial least-square model using the complete spectrum ( R 2 = 0.94 and RMSECV = 0.2). These results show the potential of Raman spectroscopy for an online detection of the pH and thus meat qualities during meat processing.

  4. Postmortem Propofol Levels: A Case of Residual Detection Long After Administration.

    PubMed

    George, Alan A; Hargrove, Veronica M; Molina, D Kimberley

    2016-03-01

    Propofol has gained notoriety in recent years because of its involvement in high-profile deaths and has increasingly become a drug of misuse and abuse particularly by health care personnel with easy access to it. In addition, propofol has also been used for more nefarious purposes such as murder and suicide. These, coupled with the drug's routine use for both major and minor medical procedures, provide ample opportunities for it to be implicated as a cause of death or contributing factor. In such instances, forensic investigators may be faced with the task of not only detecting the presence of propofol on postmortem toxicology screening, but also determining if it was indeed responsible for the decedent's demise. While propofol has a high volume of distribution, it is thought to equilibrate and be eliminated rapidly and not show significant tissue accumulation. However, this article presents a case illustrating that propofol can accumulate in the tissues and may be found up to a week after administration. This capacity to accumulate implies that postmortem detection does not necessarily confirm administration near the time of death, and further investigation needs to be undertaken to determine the timeline of events in order to rule out other factors, such as recent medical interventions, before attributing the cause of death to the presence of the drug. PMID:26513757

  5. Profile of postmortem cases conducted at a morgue of a tertiary care hospital in Kolkata.

    PubMed

    Shrivastava, Prabha; Som, Debasish; Nandy, Saswati; Saha, Indranil; Pal, Parag Baran; Ray, Tapobrata Guha; Haldar, Swaraj

    2010-11-01

    A record based cross-sectional study of postmortems performed at the mortuary attached to the forensic medicine and toxicology department of RG Kar Medical College and Hospital from March 2008 to February 2009 comprising 1900 cases was conducted to determine the sociodemographic profile and to assess the nature and cause of such deaths. Bodies of 5 foetuses were decomposed which were excluded from the study. Out of a total of 1895 postmortems analysed, 23 autopsies were performed of limbs where the subjects were alive. Out of 1872 cases in 325 (17.4%) the manner of death was natural, whereas in 1547 cases (82.6%) it was unnatural. Accidents, suicides, homicides and undetermined deaths were 63.1%, 29.8%, 2.8% and 4.3% respectively. Among the natural deaths, evidence of pulmonary tuberculosis and coronary heart disease was found in 141 (43.4%) and 124 (38.2%) cases respectively. Burn injuries (22.6%) were the most common cause of unnatural deaths and occurred in 77.4% females. Rail track injuries and road traffic injuries were responsible for 21.9% and 14% of unnatural deaths. Hanging, poisoning and self-immolation were responsible for 48.4%, 28.9% and 19.7% of suicidal deaths respectively. PMID:21510567

  6. Postmortem Study of a Magnesia-Chromite Brick from a Lead Recycling Furnace

    NASA Astrophysics Data System (ADS)

    Gregurek, D.; Reinharter, K.; Reiter, V.; Wenzl, C.; Spanring, A.

    2015-09-01

    This study provides an example of a detailed postmortem analysis carried out on a used silicate-bonded magnesia-chromite brick out of a lead recycling furnace. The magnesia-chromite brick suffered from a high chemical attack due to the process slag. The high CaO, BaO, and sulfur-bearing silicate slag, as well as a high Na2O supply from soda resulted not only in a deep-reaching infiltration of the brick microstructure but also in a severe corrosion of the brick components. Both the sintered magnesia and chromite were attacked chemically. The FactSage calculations showed the formation of high amounts of liquid phase in the infiltrated microstructure and the formation of various Na-Ca-Al-silicates. A detailed investigation of the wear mechanisms through "postmortem studies" is a crucial prerequisite for every refractory producer to understand the interactions between slag and refractory materials. The obtained information and insights serve as a basis for improving refractory materials (i.e., choice of refractories for individual process and new developments) and consequently furnace operations (i.e., prolonged furnace campaigns).

  7. Application of biochemical and X-ray diffraction analyses to establish the postmortem interval.

    PubMed

    Prieto-Castelló, M J; Hernández del Rincón, J P; Pérez-Sirvent, C; Alvarez-Jiménez, P; Pérez-Cárceles, M D; Osuna, E; Luna, A

    2007-10-25

    The determination of the date of death from bone remains is of scientific interest but also has important legal implications. The establishment of the postmortem interval (PMI) is a very complex problem because of the great number of intrinsic factors that may alter the normal course of postmortem change, such as the age, sex, constitution and previous physiological and pathological states of the subject, and external factors. In order to evaluate the utility of X-ray diffraction and the measurement of some components in dating bone remains, a total of 69 long bones from 69 different cadavers (41 males, 28 females) with a mean age of 68 years (S.D.=17.6, range 12-97) were used. The bones were removed from cement tombs of Murcia Cemetery, where they had lain for documented times of between 7 and 54 years (S.D.=11.6, mean time 17.6 years). We have studied potassium, sulphur, nitrogen, urea, total protein, phosphorus, and some X-ray diffraction (XRD) parameters related to the degree of crystallinity of the mineral component in medullar and cortical bone zones to establish which of the two provides the most useful information for calculating the PMI. In the overall analysis of our data, we believe that the use of both XRD and biochemical analyses (especially of urea, potassium and sulphur) particularly in the cortical zone of the bone could be an alternative method for dating osseous remains. PMID:17306944

  8. Neurochemistry of schizophrenia: the contribution of neuroimaging postmortem pathology and neurochemistry in schizophrenia.

    PubMed

    Dean, B

    2012-01-01

    The advent of molecular neuroimaging has greatly impacted on understanding the neurochemical changes occurring in the CNS from subjects with psychiatric disorders, especially schizophrenia. This review focuses on the outcomes from studies using positron emission tomography and single photon emission computer tomography that have measure levels of neurotransmitter receptors and transporters in the CNS from subjects with schizophrenia. One outcome from such studies is the confirmation of a number of findings using postmortem tissue, but in the case of neuroimaging, using drug na�ve and drug free subjects. These findings add weight to the argument that findings from postmortem studies are not an artifact of tissue processing or a simple drug effect. However, there are some important unique findings from studies using neuroimaging studies. These include evidence to suggest that in schizophrenia there are alterations in dopamine synthesis and release, which are not accompanied by an appropriate down-regulation of dopamine D2 receptors. There are also data that would support the notion that decreased levels of serotonin 2A receptors may be an early marker of the onset of schizophrenia. Whilst there is a clear need for on-going development of neuroimaging ligands to expand the number of targets that can be studied and to increase cohort sizes in neuroimaging studies to give power to the analyses of the resulting data, current studies show that existing neuroimaging studies have already extended our understanding of the underlying pathophysiology of psychiatric disorders such as schizophrenia. PMID:23279177

  9. Estimation of postmortem interval using the data of insulin level in the cadaver׳s blood.

    PubMed

    Kumar, Sachil; Verma, Anoop K

    2016-06-01

    An assessment of levels of Insulin in cadaveric fluids, to estimate the postmortem interval (PMI) was carried out. To profile postmortem changes of Insulin, it was extracted at different intervals i.e. (0, 3, 6, 12, 24 h), from the heart of 22 human cadavers. The cases included were the subjects of accidental deaths without any prior history of disease and their exact time of death was known. Immunoanalyzer Cobas e-411 instrument was used to detect the relationship between the amount of Insulin and PMI. Level of Insulin was measured in cardiac blood. Statically, significant correlations between levels of Insulin and PMI were studied and correlation coefficients were calculated. SPSS (version 12.0) was used for statistical analysis. Insulin levels in cadaver blood are correlated significantly with PMI with a p value of <0.001. When insulin level increases by 1 unit the duration decreases by 0.93 units. The least square regression line is: [Duration(Y)=22.71-0.93 Insulin level (X)]. PMID:26977436

  10. The rate of RNA degradation in human dental pulp reveals post-mortem interval.

    PubMed

    Poór, Viktor S; Lukács, Dénes; Nagy, Tamás; Rácz, Evelin; Sipos, Katalin

    2016-05-01

    Post-mortem interval (PMI) is the amount of time elapsed since the time of death. Over the years, many methods were developed to assess PMI, but their precision and time frame of applicability are often limited. Our present pilot study aimed to prove if RNA degradation of human dental pulp can be used for PMI estimation. RNA was isolated from the pulps of healthy wisdom teeth and premolars. RNA degradation was determined as RNA integrity number (RIN) with Agilent Bioanalyzer and subsequently by amplification of different length products by PCR after reverse transcription. The RNA integrity analysis allowed us to determine the time of post-mortem interval with high confidence level in the first 21 days. With the PCR-based method, we were able to perform a crude estimation of incubation time of teeth between 20 and 42 days post extraction. These results show that this method might be a promising new tool for PMI estimation despite the limitations. PMID:26608472

  11. Documentation of postmortem changes in salivary gland architecture and staining characteristics

    PubMed Central

    Agarwal, Swati; Chaudhary, Minal; Gawande, Madhuri; Gupta, Puneet

    2016-01-01

    Context: Estimation of time passed since death continues to be a major problem for the forensic pathologist and its determination plays an important and vital role in medico-legal cases. The histological studies on various tissues after death have been mostly confined to single organ or tissue by individual workers at different atmospheric conditions. Aims: The aim of this study is to determine the best rehydrating solution for dehydrated tissues in postmortem examination. Settings and Design: This study was specific to salivary gland tissues and certain pattern of changes were determined during postmortem time intervals using hematoxylin and eosin stain and special stains like mucicarmine and alcian blue. Materials and Methods: The study was divided into two groups. (1) Group A: Normal tissue samples (twenty normal salivary gland tissue samples left without fixation for varying periods of time). (2) Group B: Control group (twenty normal salivary gland tissue samples immediately fixed in formalin). The three different rehydrating agents used in this study were glycerol, normal saline and modified Ruffer solution. Statistical Analysis Used: Not required. Results: Modified Ruffer solution is the best when compared to glycerol and normal saline for rehydration of dehydrated tissues. Conclusions: Thus in our study we conclude that the tissue which had been dehydrated at the crime scene for a fairly long period showed better rehydration with modified Ruffer solution and yield good cellular and nuclear details. PMID:27555735

  12. Phases of global AdS black holes

    NASA Astrophysics Data System (ADS)

    Basu, Pallab; Krishnan, Chethan; Subramanian, P. N. Bala

    2016-06-01

    We study the phases of gravity coupled to a charged scalar and gauge field in an asymptotically Anti-de Sitter spacetime ( AdS 4) in the grand canonical ensemble. For the conformally coupled scalar, an intricate phase diagram is charted out between the four relevant solutions: global AdS, boson star, Reissner-Nordstrom black hole and the hairy black hole. The nature of the phase diagram undergoes qualitative changes as the charge of the scalar is changed, which we discuss. We also discuss the new features that arise in the extremal limit.

  13. Heart Wall Is Thicker on Postmortem Computed Tomography Than on Ante Mortem Computed Tomography: The First Longitudinal Study

    PubMed Central

    Okuma, Hidemi; Gonoi, Wataru; Ishida, Masanori; Shintani, Yukako; Takazawa, Yutaka; Fukayama, Masashi; Ohtomo, Kuni

    2013-01-01

    Objective To evaluate the postmortem changes of the heart wall on postmortem (PM) computed tomography (CT) in comparison with those on ante mortem CT (AMCT), and in comparison with the pathological findings, obtained in the same patients. Materials and Methods We studied 57 consecutive patients who had undergone AMCT, PMCT, and pathological autopsy in our tertiary care hospital between April 2009 and December 2010. PMCT was performed within 20 hours after death, followed by pathological autopsy. The cardiac chambers were measured at five sites on both AMCT and PMCT by two board-certified radiologists who were not provided with clinical information. The differences in heart wall thickness between AMCT with and without contrast medium, between AMCT and PMCT, and between PMCT and pathological anatomy were evaluated statistically. Confounding factors of postmortem change such as gender, presence of arteriosclerosis, the organ related to cause of death, age, and elapsed time since death were examined statistically. Results No significant differences were observed on AMCT in comparison of contrasted and non-contrasted images. The heart wall was significantly thicker on PMCT than on AMCT (p < 0.0001) at all five measurement sites. The heart wall was significantly thicker on PMCT than on pathology specimens when measured in accordance with pathological standard mensuration. However, no significant difference was observed between PMCT measurements and those of pathology specimens at any site when the papillary muscles and epicardial fat were included. No significant association was found between postmortem change in heart wall thickness and gender, presence of arteriosclerosis, the organ related to cause of death, age, or elapsed time since death. Conclusion This is the first longitudinal study to confirm greater thickness of heart wall on postmortem images compared with ante mortem images, in the same patients. Furthermore, the postmortem changes on CT were supported by

  14. Pre- and postmortem tyrannosaurid bite marks on the remains of Daspletosaurus (Tyrannosaurinae: Theropoda) from Dinosaur Provincial Park, Alberta, Canada

    PubMed Central

    Tanke, DH

    2015-01-01

    Trace marks on the bones of non-avian dinosaurs may relate to feeding by large carnivores or as a result of combat. Here the cranium and mandible of a specimen of Daspletosaurus are described that show numerous premortem injuries with evidence of healing and these are inferred to relate primarily to intraspecific combat. In addition, postmortem damage to the mandible is indicative of late stage carcass consumption and the taphonomic context suggests that this was scavenging. These postmortem bites were delivered by a large bodied tyrannosaurid theropod and may have been a second Daspletosaurus, and thus this would be an additional record of tyrannosaurid cannibalism. PMID:25870775

  15. Pre- and postmortem tyrannosaurid bite marks on the remains of Daspletosaurus (Tyrannosaurinae: Theropoda) from Dinosaur Provincial Park, Alberta, Canada.

    PubMed

    Hone, Dwe; Tanke, D H

    2015-01-01

    Trace marks on the bones of non-avian dinosaurs may relate to feeding by large carnivores or as a result of combat. Here the cranium and mandible of a specimen of Daspletosaurus are described that show numerous premortem injuries with evidence of healing and these are inferred to relate primarily to intraspecific combat. In addition, postmortem damage to the mandible is indicative of late stage carcass consumption and the taphonomic context suggests that this was scavenging. These postmortem bites were delivered by a large bodied tyrannosaurid theropod and may have been a second Daspletosaurus, and thus this would be an additional record of tyrannosaurid cannibalism. PMID:25870775

  16. Contribution of postmortem muscle biochemistry to the delivery of consistent meat quality with particular focus on the calpain system.

    PubMed

    Koohmaraie, M; Geesink, G H

    2006-09-01

    Tenderness has been repeatedly reported as the most important quality aspect of meat. However, a number of studies have shown that a significant portion of retail meat can be considered tough. As a consequence, a significant consumer segment is willing to pay a premium for guaranteed tender meat. However, apart from measuring the shear force, there is no reliable method to predict tenderness. Most of the branded meat programs therefore attempt to ensure eating quality by controlling some of the factors that affect tenderness. Meat tenderness is determined by the amount and solubility of connective tissue, sarcomere shortening during rigor development, and postmortem proteolysis of myofibrillar and myofibrillar-associated proteins. Given the effect of postmortem proteolysis on the muscle ultrastructure, titin and desmin are likely key substrates that determine meat tenderness. A large number of studies have shown that the calpain proteolytic system plays a central role in postmortem proteolysis and tenderization. In skeletal muscle, the calpain system consists of at least three proteases, μ-calpain, m-calpain and calpain 3, and an inhibitor of μ- and m-calpain, calpastatin. When activated by calcium, the calpains not only degrade subtrates, but also autolyze, leading to loss of activity. m-Calpain does not autolyze in postmortem muscle and is therefore not involved in postmortem tenderization. Results from a number of studies, including a study on calpain 3 knockout mice, have shown that calpain 3 is also not involved in postmortem proteolysis. However, a large number of studies, including a study on μ-calpain knockout mice, have shown that μ-calpain is largely, if not solely, responsible for postmortem tenderization. Research efforts in this area should, therefore, focus on elucidation of regulation of μ-calpain activity in postmortem muscle. Discovering the mechanisms of μ-calpain activity regulation and methods to promote μ-calpain activity should have a

  17. Postmortem detection of 25I-NBOMe [2-(4-iodo-2,5-dimethoxyphenyl)-N-[(2-methoxyphenyl)methyl]ethanamine] in fluids and tissues determined by high performance liquid chromatography with tandem mass spectrometry from a traumatic death

    PubMed Central

    Poklis, Justin L.; Devers, Kelly G.; Arbefeville, Elise F.; Pearson, Julia M.; Houston, Eric; Poklis, Alphonse

    2014-01-01

    We present a traumatic fatality of a 19-year-old man who had ingested blotter paper containing 25INBOMe [2-(4-iodo-2,5-dimethoxyphenyl)-N-[(2-methoxyphenyl)methyl]ethanamine]. Postmortem specimens were analyzed by high performance liquid chromatography with tandem mass spectrometry (HPLC/MS/MS). Toxicology findings for fluids based upon blood or urine calibrators were as follows: peripheral blood, 405 pg/mL; heart blood, 410 pg/mL; urine, 2.86 ng/mL; and vitreous humor, 99 pg/mL. While findings based upon the method of standard additions were: gastric contents, 7.1 μg total; bile, 10.9 ng/g; brain, 2.54 ng/g and liver, 7.2 ng/g. To our knowledge the presented case is the first postmortem case of 25I-NBOMe intoxication documented by toxicological analysis of tissues and body fluids. PMID:24215811

  18. The forecaster's added value

    NASA Astrophysics Data System (ADS)

    Turco, M.; Milelli, M.

    2009-09-01

    skill scores of two competitive forecast. It is important to underline that the conclusions refer to the analysis of the Piemonte operational alert system, so they cannot be directly taken as universally true. But we think that some of the main lessons that can be derived from this study could be useful for the meteorological community. In details, the main conclusions are the following: - despite the overall improvement in global scale and the fact that the resolution of the limited area models has increased considerably over recent years, the QPF produced by the meteorological models involved in this study has not improved enough to allow its direct use, that is, the subjective HQPF continues to offer the best performance; - in the forecast process, the step where humans have the largest added value with respect to mathematical models, is the communication. In fact the human characterisation and communication of the forecast uncertainty to end users cannot be replaced by any computer code; - eventually, although there is no novelty in this study, we would like to show that the correct application of appropriated statistical techniques permits a better definition and quantification of the errors and, mostly important, allows a correct (unbiased) communication between forecasters and decision makers.

  19. Mystery cloud of AD 536

    NASA Technical Reports Server (NTRS)

    Stothers, R. B.

    1984-01-01

    The possible cause of the densest and most persistent dry fog on record, which was observed in Europe and the Middle East during AD 536 and 537, is discussed. The fog's long duration toward the south and the high sulfuric acid signal detected in Greenland in ice cores dated around AD 540 support the theory that the fog was due to the explosion of the Rabaul volcano, the occurrence of which has been dated at about AD 540 by the radiocarbon method.

  20. Imaging the Alzheimer Brain

    PubMed Central

    Ashford, J. Wesson; Salehi, Ahmad; Furst, Ansgar; Bayley, Peter; Frisoni, Giovanni B.; Jack, Clifford R.; Sabri, Osama; Adamson, Maheen M.; Coburn, Kerry L.; Olichney, John; Schuff, Norbert; Spielman, Daniel; Edland, Steven D.; Black, Sandra; Rosen, Allyson; Kennedy, David; Weiner, Michael; Perry, George

    2013-01-01

    This supplement to the Journal of Alzheimer's Disease contains more than half of the chapters from The Handbook of Imaging the Alzheimer Brain, which was first presented at the International Conference on Alzheimer's Disease in Paris, in July, 2011. While the Handbook contains 27 chapters that are modified articles from 2009, 2010, and 2011 issues of the Journal of Alzheimer's Disease, this supplement contains the 31 new chapters of that book and an introductory article drawn from the introductions to each section of the book. The Handbook was designed to provide a multilevel overview of the full field of brain imaging related to Alzheimer's disease (AD). The Handbook, as well as this supplement, contains both reviews of the basic concepts of imaging, the latest developments in imaging, and various discussions and perspectives of the problems of the field and promising directions. The Handbook was designed to be useful for students and clinicians interested in AD as well as scientists studying the brain and pathology related to AD. PMID:21971448

  1. Postmortem aging can significantly enhance water-holding capacity of broiler pectoralis major muscle measured by the salt-induced swelling/centrifuge method

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Water-holding capacity (WHC) is one of the most important functional properties of fresh meat and can be significantly affected by postmortem muscle changes. Two experiments were carried out to evaluate the effects of postmortem aging on WHC of broiler pectoralis (p.) major muscle indicated with % s...

  2. AdS Branes from Partial Breaking of Superconformal Symmetries

    SciTech Connect

    Ivanov, E.A.

    2005-10-01

    It is shown how the static-gauge world-volume superfield actions of diverse superbranes on the AdS{sub d+1} superbackgrounds can be systematically derived from nonlinear realizations of the appropriate AdS supersymmetries. The latter are treated as superconformal symmetries of flat Minkowski superspaces of the bosonic dimension d. Examples include the N = 1 AdS{sub 4} supermembrane, which is associated with the 1/2 partial breaking of the OSp(1|4) supersymmetry down to the N = 1, d = 3 Poincare supersymmetry, and the T-duality related L3-brane on AdS{sub 5} and scalar 3-brane on AdS{sub 5} x S{sup 1}, which are associated with two different patterns of 1/2 breaking of the SU(2, 2|1) supersymmetry. Another (closely related) topic is the AdS/CFT equivalence transformation. It maps the world-volume actions of the codimension-one AdS{sub d+1} (super)branes onto the actions of the appropriate Minkowski (super)conformal field theories in the dimension d.

  3. AdS5 backgrounds with 24 supersymmetries

    NASA Astrophysics Data System (ADS)

    Beck, S.; Gutowski, J.; Papadopoulos, G.

    2016-06-01

    We prove a non-existence theorem for smooth AdS 5 solutions with connected, compact without boundary internal space that preserve strictly 24 supersymmetries. In particular, we show that D = 11 supergravity does not admit such solutions, and that all such solutions of IIB supergravity are locally isometric to the AdS 5 × S 5 maximally supersymmetric background. Furthermore, we prove that (massive) IIA supergravity also does not admit such solutions, provided that the homogeneity conjecture for massive IIA supergravity is valid. In the context of AdS/CFT these results imply that if gravitational duals for strictly mathcal{N}=3 superconformal theories in 4-dimensions exist, they are either singular or their internal spaces are not compact.

  4. Entanglement temperature and perturbed AdS3 geometry

    NASA Astrophysics Data System (ADS)

    Levine, G. C.; Caravan, B.

    2016-06-01

    Generalizing the first law of thermodynamics, the increase in entropy density δ S (x ) of a conformal field theory (CFT) is proportional to the increase in energy density, δ E (x ) , of a subsystem divided by a spatially dependent entanglement temperature, TE(x ) , a fixed parameter determined by the geometry of the subsystem, crossing over to thermodynamic temperature at high temperatures. In this paper we derive a generalization of the thermodynamic Clausius relation, showing that deformations of the CFT by marginal operators are associated with spatial temperature variations, δ TE(x ) , and spatial energy correlations play the role of specific heat. Using AdS/CFT duality we develop a relationship between a perturbation in the local entanglement temperature of the CFT and the perturbation of the bulk AdS metric. In two dimensions, we demonstrate a method through which direct diagonalizations of the boundary quantum theory may be used to construct geometric perturbations of AdS3 .

  5. The difficult task of assessing perimortem and postmortem fractures on the skeleton: a blind text on 210 fractures of known origin.

    PubMed

    Cappella, Annalisa; Amadasi, Alberto; Castoldi, Elisa; Mazzarelli, Debora; Gaudio, Daniel; Cattaneo, Cristina

    2014-11-01

    The distinction between perimortem and postmortem fractures is an important challenge for forensic anthropology. Such a crucial task is presently based on macro-morphological criteria widely accepted in the scientific community. However, several limits affect these parameters which have not yet been investigated thoroughly. This study aims at highlighting the pitfalls and errors in evaluating perimortem or postmortem fractures. Two trained forensic anthropologists were asked to classify 210 fractures of known origin in four skeletons (three victims of blunt force trauma and one natural death) as perimortem, postmortem, or dubious, twice in 6 months in order to assess intraobserver error also. Results show large errors, ranging from 14.8 to 37% for perimortem fractures and from 5.5 to 14.8% for postmortem ones; more than 80% of errors concerned trabecular bone. This supports the need for more objective and reliable criteria for a correct assessment of peri- and postmortem bone fractures. PMID:24990801

  6. Brain abscess

    MedlinePlus

    ... with certain heart disorders, may receive antibiotics before dental or other procedures to help reduce the risk of infection. Alternative Names Abscess - brain; Cerebral abscess; CNS abscess Images Amebic brain ...

  7. Brain Diseases

    MedlinePlus

    The brain is the control center of the body. It controls thoughts, memory, speech, and movement. It regulates the function of many organs. When the brain is healthy, it works quickly and automatically. However, ...

  8. Brain surgery

    MedlinePlus

    Craniotomy; Surgery - brain; Neurosurgery; Craniectomy; Stereotactic craniotomy; Stereotactic brain biopsy; Endoscopic craniotomy ... Before surgery, the hair on part of the scalp is shaved and the area is cleaned. The doctor makes ...

  9. Brain Health

    MedlinePlus

    ... exercise, diet and nutrition, cognitive activity, and social engagement — can help keep your body and brain ... Stay Mentally Active > Mentally challenging activities and social engagement may support brain health. Learn More Plan ahead ...

  10. Using ultrasound to estimate brain size in the cephalopod Octopus vulgaris cuvier in vivo.

    PubMed

    Grimaldi, Anna Maria; Agnisola, Claudio; Fiorito, Graziano

    2007-12-01

    Ultrasound imaging was applied, for the first time, in the examination of the central nervous system of the cephalopod mollusc Octopus vulgaris, an invertebrate. Goals of this study were: i. to reveal and measure the cerebral masses in vivo, in their anatomical position; ii. to evaluate and compare the dimensions of the different parts of the octopus brain in vivo and postmortem, and iii. to test the reproducibility of the ultrasound method both in reaching a given sonographic plane in the same individual at two different times and in evaluating potential changes in brain size due to animal growth. Our results show that ultrasonography is a reliable method to measure the various parts of the octopus brain. Sonographic measurements of the brain masses in vivo were correlated with those determined postmortem. In addition, brain size estimation is reproducible via ultrasound: no significant difference resulted when measurements of the same brain were taken over consecutive days. Furthermore, when the time lapse between the two sonographic examinations was long enough (30 days), we were able to detect changes in brain dimensions in the same octopus. PMID:17964558

  11. The Brain.

    ERIC Educational Resources Information Center

    Hubel, David H.

    1979-01-01

    This article on the brain is part of an entire issue about neurobiology and the question of how the human brain works. The brain as an intricate tissue composed of cells is discussed based on the current knowledge and understanding of its composition and structure. (SA)

  12. Brain Aneurysm

    MedlinePlus

    A brain aneurysm is an abnormal bulge or "ballooning" in the wall of an artery in the brain. They are sometimes called berry aneurysms because they ... often the size of a small berry. Most brain aneurysms produce no symptoms until they become large, ...

  13. Lorentzian AdS geometries, wormholes, and holography

    SciTech Connect

    Arias, Raul E.; Silva, Guillermo A.; Botta Cantcheff, Marcelo

    2011-03-15

    We investigate the structure of two-point functions for the quantum field theory dual to an asymptotically Lorentzian Anti de Sitter (AdS) wormhole. The bulk geometry is a solution of five-dimensional second-order Einstein-Gauss-Bonnet gravity and causally connects two asymptotically AdS spacetimes. We revisit the Gubser-Klebanov-Polyakov-Witten prescription for computing two-point correlation functions for dual quantum field theories operators O in Lorentzian signature and we propose to express the bulk fields in terms of the independent boundary values {phi}{sub 0}{sup {+-}} at each of the two asymptotic AdS regions; along the way we exhibit how the ambiguity of normalizable modes in the bulk, related to initial and final states, show up in the computations. The independent boundary values are interpreted as sources for dual operators O{sup {+-}} and we argue that, apart from the possibility of entanglement, there exists a coupling between the degrees of freedom living at each boundary. The AdS{sub 1+1} geometry is also discussed in view of its similar boundary structure. Based on the analysis, we propose a very simple geometric criterion to distinguish coupling from entanglement effects among two sets of degrees of freedom associated with each of the disconnected parts of the boundary.

  14. Self-dual warped AdS3 black holes

    NASA Astrophysics Data System (ADS)

    Chen, Bin; Ning, Bo

    2010-12-01

    We study a new class of solutions of three-dimensional topological massive gravity. These solutions can be taken as nonextremal black holes, with their extremal counterparts being discrete quotients of spacelike warped AdS3 along the U(1)L isometry. We study the thermodynamics of these black holes and show that the first law is satisfied. We also show that for consistent boundary conditions, the asymptotic symmetry generators form only one copy of the Virasoro algebra with central charge cL=(4νℓ)/(G(ν2+3)), with which the Cardy formula reproduces the black hole entropy. We compute the real-time correlators of scalar perturbations and find a perfect match with the dual conformal field theory (CFT) predictions. Our study provides a novel example of warped AdS/CFT correspondence: the self-dual warped AdS3 black hole is dual to a CFT with nonvanishing left central charge. Moreover, our investigation suggests that the quantum topological massive gravity asymptotic to the same spacelike warped AdS3 in different consistent ways may be dual to different two-dimensional CFTs.

  15. Metabolic profiling of Alzheimer's disease brains

    NASA Astrophysics Data System (ADS)

    Inoue, Koichi; Tsutsui, Haruhito; Akatsu, Hiroyasu; Hashizume, Yoshio; Matsukawa, Noriyuki; Yamamoto, Takayuki; Toyo'Oka, Toshimasa

    2013-08-01

    Alzheimer's disease (AD) is an irreversible, progressive brain disease and can be definitively diagnosed after death through an examination of senile plaques and neurofibrillary tangles in several brain regions. It is to be expected that changes in the concentration and/or localization of low-molecular-weight molecules are linked to the pathological changes that occur in AD, and determining their identity would provide valuable information regarding AD processes. Here, we propose definitive brain metabolic profiling using ultra-performance liquid chromatography coupled with electrospray time-of-flight mass spectrometry analysis. The acquired data were subjected to principal components analysis to differentiate the frontal and parietal lobes of the AD/Control groups. Significant differences in the levels of spermine and spermidine were identified using S-plot, mass spectra, databases and standards. Based on the investigation of the polyamine metabolite pathway, these data establish that the downstream metabolites of ornithine are increased, potentially implicating ornithine decarboxylase activity in AD pathology.

  16. Left Brain. Right Brain. Whole Brain

    ERIC Educational Resources Information Center

    Farmer, Lesley S. J.

    2004-01-01

    As the United States student population is becoming more diverse, library media specialists need to find ways to address these distinctive needs. However, some of these differences transcend culture, touching on variations in the brain itself. Most people have a dominant side of the brain, which can affect their personality and learning style.…

  17. Sequencing CYP2D6 for the detection of poor-metabolizers in post-mortem blood samples with tramadol.

    PubMed

    Fonseca, Suzana; Amorim, António; Costa, Heloísa Afonso; Franco, João; Porto, Maria João; Santos, Jorge Costa; Dias, Mário

    2016-08-01

    Tramadol concentrations and analgesic effect are dependent on the CYP2D6 enzymatic activity. It is well known that some genetic polymorphisms are responsible for the variability in the expression of this enzyme and in the individual drug response. The detection of allelic variants described as non-functional can be useful to explain some circumstances of death in the study of post-mortem cases with tramadol. A Sanger sequencing methodology was developed for the detection of genetic variants that cause absent or reduced CYP2D6 activity, such as *3, *4, *6, *8, *10 and *12 alleles. This methodology, as well as the GC/MS method for the detection and quantification of tramadol and its main metabolites in blood samples was fully validated in accordance with international guidelines. Both methodologies were successfully applied to 100 post-mortem blood samples and the relation between toxicological and genetic results evaluated. Tramadol metabolism, expressed as its metabolites concentration ratio (N-desmethyltramadol/O-desmethyltramadol), has been shown to be correlated with the poor-metabolizer phenotype based on genetic characterization. It was also demonstrated the importance of enzyme inhibitors identification in toxicological analysis. According to our knowledge, this is the first study where a CYP2D6 sequencing methodology is validated and applied to post-mortem samples, in Portugal. The developed methodology allows the data collection of post-mortem cases, which is of primordial importance to enhance the application of these genetic tools to forensic toxicology and pathology. PMID:26926096

  18. Sol-gel immobilized luciferase-based ATP biosensor for meat quality determination in postmortem pig muscle

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Inferior pork quality results from a rapid rate of muscle metabolism that is stimulated by ATP depletion early postmortem. The objectives of this study were 1) to test the hypothesis that muscle ATP as measured by a luciferase assay could be used for predicting fresh pork quality, and 2) to explore ...

  19. Postmortem findings in four south American sea lions (Otaria byronia) from an urban colony in Valdivia, Chile.

    PubMed

    Sepúlveda, Maximiliano A; Seguel, Mauricio; Alvarado-Rybak, Mario; Verdugo, Claudio; Muñoz-Zanzi, Claudia; Tamayo, Rafael

    2015-01-01

    We performed postmortem examination on four South American sea lions (Otaria byronia) from an urban colony in Valdivia, Chile. Chronic leptospirosis and suspected morbillivirus-like infection were diagnosed in one individual. Antibodies against Toxoplasma gondii and the zoonotic helminthes Contracaecum sp., Pseudoterranova sp., and Diphyllobothrium sp. were also detected. PMID:25380367

  20. Measurement of β-tryptase in postmortem serum, pericardial fluid, urine and vitreous humor in the forensic setting.

    PubMed

    Comment, Lionel; Reggiani Bonetti, Luca; Mangin, Patrice; Palmiere, Cristian

    2014-07-01

    In the realm of forensic pathology, β-tryptase measurement for diagnostic purposes is performed in postmortem serum obtained from femoral blood. This may be partially or completely unavailable in some specific cases, such as infant autopsies and severely damaged bodies. The aim of this study was to investigate the usefulness of determining β-tryptase levels for diagnostic purposes in alternative biological samples. Urine, vitreous humor and pericardial fluid were selected and measured in 94 subjects including: fatal anaphylaxis following contrast material administration (6 cases), hypothermia (10 cases), diabetic ketoacidosis (10 cases), gunshot suicide (10 cases), heroin injection-related deaths (18 cases), trauma (10 cases), sudden death with minimal coronary atherosclerosis (10 cases), severe coronary atherosclerosis without myocardial infarction (10 cases) and severe coronary atherosclerosis with myocardial infarction (10 cases). Postmortem serum and pericardial fluid β-tryptase levels higher than the clinical reference value (11.4ng/ml) were systematically identified in fatal anaphylaxis following contrast material administration and 6 cases unrelated to anaphylaxis. β-tryptase concentrations in urine and vitreous humor were lower than the clinical reference value in all cases included in this study. Determination of β-tryptase in pericardial fluid appears to be a possible alternative to postmortem serum in the early postmortem period when femoral blood cannot be collected during autopsy and biochemical investigations are required to objectify increased β-tryptase levels. PMID:24795293