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Apomorphine-induced aggressive behaviour and post-mortem monoamine content in male Wistar rats.

The aim of this study was to investigate the monoamine content in post-mortem brain samples of control, apomorphine-aggressive, and apomorphine-non-aggressive adult male Wistar rats. The repeated apomorphine (1.0 mg/kg, (s.c.) once daily during 2 weeks) gradually induced aggressive behaviour in 18 animals out of 24. No unidirectional changes in the brain monoamine contents in four regions (frontal cortex, striatum, hippocampus, and hypothalamus) were detected as measured by high pressure liquid chromatography-electrochemical detection. In conclusion, our present experiment demonstrates that the development and intensity of apomorphine-induced aggressive behaviour do not correlate with the brain post-mortem monoamine content.

Aggression↗

Metabotropic glutamate receptor protein expression in the prefrontal cortex and striatum in schizophrenia.

We investigated the expression of metabotropic glutamate receptors (mGluR) in the prefrontal cortex (PFC) and striatum in schizophrenia. mGluRs modulate the release and reuptake of synaptic glutamate and mediate some molecular correlates of neuroplasticity, including long-term potentiation. The mGluRs are expressed widely in the PFC and striatum, regions often implicated in the pathophysiology of schizophrenia. Thus, we hypothesized that abnormal expression of mGluRs might contribute to glutamatergic dysfunction observed in the PFC and striatum in schizophrenia. Accordingly, we measured the expression of metabotropic glutamate receptors (mGluRs) in Brodmann areas 9, 11, 32, and 46 in the prefrontal cortex (PFC) and the caudate, putamen, and nucleus accumbens in schizophrenia (16 cases, 9 controls) by Western blot analysis. We found an increase in the expression of mGluR1a and mGluR2/3 immunoreactivity in the PFC in schizophrenia, while no changes in the expression of mGluR4a or mGluR5 were detected in this region. In the striatum we found no changes in the expression of any of the mGluRs studied. These results suggest that alterations of mGluR1a and mGluR2/3 expression in the PFC may contribute to the pathophysiology of schizophrenia, and support targeting these receptors for the generation of novel treatment modalities for this disabling illness.

Aged↗

Dietary manipulation of pro- and macroglycogen in porcine skeletal muscle.

The aim of the study was to investigate how feeding-induced changes in muscle glycogen stores affect the ratio of between the glycogen pools, pro- and macroglycogen. Pro- and macroglycogen content were determined in longissumus muscle from slaughter pigs subjected to a feeding strategy known to reduce total glycogen stores. Furthermore, early postslaughter glycolysis of the two glycogen forms was determined. The feeding strategy involved a diet (GLYRED diet) with a low digestible carbohydrate (5%)/high fat (18%) content, which was fed to the pigs the last 3 wk before harvest. A control group was fed a standard pig diet (49% digestible carbohydrate/5% fat). Total glycogen was reduced by 48 micromol/g dry weight (d.w.) in GLYRED pigs during the 3-wk feeding period. This was mainly due to a reduction in macroglycogen of 42 micromol/g d.w. During postmortem glycolysis the proglycogen appeared to be degraded in favor of macroglycogen. Moreover, total glycogen was degraded to a larger extent in muscle from the control pigs compared with muscle from GLYRED pigs. This difference was due to a significantly greater degradation of proglycogen in the control pigs. In conclusion, the results support earlier studies suggesting that proglycogen and macroglycogen are different glycogen pools that have different functions. Furthermore, the results show that the muscle glycogen pools can be manipulated through diet and that proglycogen is degraded in favor of macroglycogen under the anaerobic conditions postmortem.

Animal Feed↗

[The diagnosis of intrauterine asphyxia by the lipid content in the lungs of the cadavers of newborn infants using fresh and putrefied material].

Lipid content was measured in lung tissue of live and stillborn newborns with and without putrefactive changes by biochemical method of lipid extraction by hexane from dried fragments. Biochemical detection of high levels of lipids in pulmonary tissue from newborns both with and without putrefactive changes was found to be an evidence of intrauterine asphyxia caused by aspiration of amniotic fluid, and, hence, this method helped assess the contribution of intrauterine asphyxia to the origin and cause of death. The results are of paramount importance for forensic medicine, particularly so in cases when putrefied corpses of newborns have to be examined and there is no data on the course of pregnancy and labor.

Autopsy↗

Evaluation of the correlation between time corpses spent in in-ground graves and findings at exhumation.

To determine how long pathological findings persist after burial and which factors play a role in decomposition of a corpse, we evaluated all bodies exhumed under the auspices of the Institute of Legal Medicine at the Hannover Medical School between 1978 and 1997. A total of 87 exhumations (54 men, 33 women) were performed in this period. The time bodies remained buried varied between 5 days and 16.8 years (mean 1.5 years, median 2.3 months). Fifty-six percent of the bodies were exhumed after at most 3 months, 10% remained buried for greater than 3 years. Pathomorphological changes of the soft tissues and the internal organs remained evident after several months, in some cases after several years of burial. Overall, it was possible to evaluate internal organs after 5 years of burial. Bodies became mostly decomposed after approximately 8 years at the earliest, although it was still possible to evaluate some soft tissue remnants after 16.8 years. In stepwise logistic regression, both the length of time the body was buried (p < 0.00005) and the time of year (p < 0.0019) clearly affected the rate of physical change. The variables of sex (p = 0.33), age (p = 0.61) and changes in the integrity of the body before burial (trauma, autopsy before burial; p = 0.15) did not influence the physical state of the body after exhumation. Our data show that much information may be gained from an exhumation even after significant time has passed since burial.

Adolescent↗

Feather retention force in broilers ante-, peri-, and post-mortem as influenced by carcass orientation, angle of extraction, and slaughter method.

Stunning and slaughter trials were conducted to evaluate the influence of carcass orientation (inverted or supine), angle of feather extraction (parallel or perpendicular to the carcass surface), and slaughter method (exsanguination without or with spinal cord transection) on feather retention force (FRF) in commercial broilers sampled ante-, peri-, and post-mortem. The pectoral, sternal, and femoral feather tracts were sampled before and after stunning contralaterally, with a maximum indicating force gauge, from broilers suspended on a shackle (inverted) or laying on a table (supine). For all trials and sample periods FRF was consistently greater in the femoral area (547 to 679 g) than in the pectoral area (273 to 391 g), with the sternal feather tract requiring the least force at 246 to 343 g. Feathers extracted parallel to the carcass resulted in consistently greater FRF (9 to 29%) than feathers extracted at a perpendicular angle, at all sample periods. Broilers suspended on shackles ante- and peri-mortem had higher FRF values (5 to 30%) than those restrained in shackles in a supine position on a table. Other parameters resulted in minor and inconsistent alterations in FRF. Electrical stunning, when not followed by bleeding, resulted in small reductions in FRF (up to 7%). Bleeding after stunning without or with spinal cord transection resulted in variable peri-mortem FRF changes (+7 to -11% and +11 to -11%, respectively). Only in the pectoral feather tract was there a significant increase (5 to 6%) in FRF as broilers went from the ante- to peri-mortem state. At 2 and 6 min after stunning and initiation of exsanguination, post-mortem FRF was unaffected by carcass orientation for the pectoral and femoral tracts.

Abattoirs↗

Time-dependent changes in donor brain death related processes.

Donor brain death (BD) affects kidney function and survival after transplantation. Studies on brain dead kidney donors indicate that, besides inflammation and coagulation, cytoprotective gene expression is activated as well. Here, we evaluated in a time-course experiment progression of these renal BD-related processes. Animals were sacrificed 0.5, 1, 2 or 4 h after BD and compared to sham-operated controls. Proinflammatory genes (E-selectin, MCP-1, II-6) were massively up-regulated (p < 0.05) already 0.5 h after BD. Inducers of proinflammatory gene expression were either activated (NF-kappaB) or induced in expression (Egr-1) after 0.5 h of BD. Increased numbers of infiltrating granulocytes were seen in the interstitium from 0.5 h on. Also, expression of protective genes HO-1 and HSP70 were increased within 0.5 h. Remarkably, reactive oxygen species formation was detectable only in the later phase of BD. Among 14 measured serum cytokines, MCP-1 and KC-protein were significantly elevated from 0.5 h on. In conclusion, a fast induction of proinflammatory and stress-induced protective processes in brain dead donor kidneys was demonstrated, probably triggered by changes occurring during BD induction. Importantly, hypoxia appeared not to be one of the initial triggers, and early increased systemic levels of chemokines MCP-1 and KC may be regarded as the starting point for the inflammatory cascade in brain dead donor kidneys.

Animals↗

Neocortical neuronal, synaptic, and glial loss in multiple sclerosis.

BACKGROUND: Recent pathologic investigations have shown that neocortical lesions are frequent in multiple sclerosis (MS). Structural MRI has shown that neocortical atrophy occurs early and can be substantial, but the specific substrate for this atrophy has not been defined quantitatively. OBJECTIVE: To investigate cortical thickness as well as neuronal, glial, and synaptic densities in MS. METHODS: We studied brain samples from 22 patients with MS and 17 control subjects. Neocortical lesions and cortical thickness were assessed on sections stained for myelin basic protein. Neuronal, glial, and synaptic densities were measured in type I leukocortical lesions, nonlesional neocortex, and non-MS control cortex. Immunoautoradiography was used to quantify synaptic densities. RESULTS: Neocortical lesions were common in patients with MS. Subpial type III (44%) and leukocortical type I (38%) lesions were more abundant than intracortical type II (18%) lesions. An overall relative neocortical thinning of 10% (p = 0.016) was estimated for the patients. Within the type I lesions, we found evidence for substantial cell (glial, 36%, p = 0.001; neuronal, 10%, p = 0.032) and synaptic (47% decrease in synaptophysin, p = 0.001) loss. Nonlesional neocortex did not show significant relative changes in neuronal, glial, or synaptic density. CONCLUSIONS: Neocortical neuronal and glial degeneration is significant in multiple sclerosis. Synaptic loss was particularly striking in the neocortical lesions, which should make a major independent contribution to the expression of pathology. New therapies should be directed toward limiting this damage.

Adult↗

Systematic investigation of degradation effects on spin-spin relaxation times in mouse-liver by low resolution NMR.

Despite numerous work on spin-lattice (T1) relaxation in vitro, not much attention has been paid on spin-spin (T2) relaxation until now. In this study we are presenting spin-spin relaxation time measurements of mouse liver tissue in order to estimate the time-after-excision effects. The post mortem behaviour of excised tissue was investigated up to four hours in intervals of about nine minutes. The time course of liver T2 was determined for different temperatures (4 degrees - 40 degrees C) for female mice. In order to describe the similar behaviour of T2 and pH changes in mouse liver after excision, we are suggesting an empirical model to correlate this data. In contrast to T1 results published recently, we found no significant differences in liver T2 time course after excision due to different physiological states like sex, starvation or circadian rhythm. T1/T2-behaviour after tissue excision is discussed in an attempt to separate various relaxation mechanisms.

Animals↗

[Experimental poisoning with gaseous hydrocarbons: changes in concentrations of propane and butane in the lung and adipose tissue in relation to the time of death].

Postmortal changes of propane, butane and iso-butane concentration in the lung and fat of mice exposed to lethal intoxication with commercial liquid gas are studied. The hydrocarbon tissue concentrations after exposure were determined by gas liquid chromatography. The hydrocarbons progressively decreased in the lung and disappeared, depending on the degree of putrefaction; even in case of remarkable putrefaction, it was still possible to detect them in the fat tissue.

Adipose Tissue↗

[Putrefaction-induced changes in the concentration and temporal detectibility of carbon monoxide in cadaveric blood samples].

Eighty-five blood samples with COHb concentrations of 40% and 70% were allowed to putrefy in order to measure the time-dependent changes in COHb values. The samples not hermetically closed had been stored at 6 degrees C and 20 degrees C. GC and photometric methods were applied. Two graphs show that after 15 days (40% COHb) and after 30 days (70% COHb), the COHb concentrations decreased to half at 20 degrees C. Corresponding decreases at a storage at 6 degrees C could be observed after 1 year. Further investigations excluded the formation of new CO.

Carbon Monoxide Poisoning↗

Immunohistological investigations of autopsied carotid bodies and their application to diagnosing strangulation.

Using immunohistochemical staining, the histological changes and the presence of neuropeptides (enkephalin and VIP) in the carotid body have been investigated in medico-legal autopsy cases, especially asphyxia cases. Only in cases of manual and/or ligature strangulation cases that sustained a force near the carotid body, were the chief cells mainly lightly stained, indicating that they had been "active" cells. Furthermore, these cells and their nuclei were enlarged in comparison to the chief carotid body cells in other autopsy groups. It was thus felt that these changes had resulted from the force that had directly affected the carotid body. Based on these findings, it was concluded that immunohistochemical investigation of the carotid body offers a useful possibility for diagnosing manual asphyxia, especially in autopsy cases involving strangulation.

Adolescent↗

Neurotensin in human brain: regional distribution and effects of neurological illness.

The regional distribution of neurotensin-like immunoreactivity was investigated in normal human brain and in brains of patients who had died with neurological illness. In Huntington's disease, neurotensin was increased in the pallidum, whilst in Parkinson's disease no significant changes in neurotensin content were observed. Similarly no changes were found in the telencephalic neurotensin content in senile dementia of the Alzheimer type. High levels of neurotensin-like immunoreactivity were detected in lumbar cerebrospinal fluid from patients and the characterization of the immunoreactive material by high-performance liquid chromatography showed it to be indistinguishable from synthetic neurotensin.

Aged↗

Patterns of gene expression in the frontal cortex discriminate alcoholic from nonalcoholic individuals.

Alcohol dependence is characterized by tolerance, physical dependence, and craving. The neuroadaptations underlying these effects of chronic alcohol abuse are likely due to altered gene expression. Previous gene expression studies using human post-mortem brain demonstrated that several gene families were altered by alcohol abuse. However, most of these changes in gene expression were small. It is not clear if gene expression profiles have sufficient power to discriminate control from alcoholic individuals and how consistent gene expression changes are when a relatively large sample size is examined. In the present study, microarray analysis (approximately 47,000 elements) was performed on the superior frontal cortex of 27 individual human cases (14 well characterized alcoholics and 13 matched controls). A partial least squares statistical procedure was applied to identify genes with altered expression levels in alcoholics. We found that genes involved in myelination, ubiquitination, apoptosis, cell adhesion, neurogenesis, and neural disease showed altered expression levels. Importantly, genes involved in neurodegenerative diseases such as Alzheimer's disease were significantly altered suggesting a link between alcoholism and other neurodegenerative conditions. A total of 27 genes identified in this study were previously shown to be changed by alcohol abuse in previous studies of human post-mortem brain. These results revealed a consistent re-programming of gene expression in alcohol abusers that reliably discriminates alcoholic from non-alcoholic individuals.

Adult↗

An analysis of factors influencing measurements of dopamine, noradrenaline, glutamate decarboxylase and choline acetylase in human post-mortem brain tissue.

Measurements have been made of dopamine, noradrenaline, glutamate decarboxylase (GAD) and choline acetylase (CAT) in a variety of regions from human post-mortem brain tissue, and the results analysed as a function of ante-mortem and post-mortem factors which may influence such measurements. The agonal status of the patient emerged as a major influence on the post-mortem measurement of GAD activity, without significantly affecting the other biochemical parameters. Of the other ante-mortem factors investigated, there appeared to be no differences between male and female, no circadian fluctuations, and few significant age-related changes, in any of the biochemical parameters measured in different brain regions. Moreover, the results indicated that the enzymes GAD and CAT are remarkably stable in human brain during routine post-mortem handling. Similar findings were made for dopamine and noradrenaline, although a substantial loss of both catecholamines probably occurs in the first few hours after death.

Adolescent↗

Pathology of asthma.

Asthma is a clinically complex condition but at present the pathologist recognises only one disease process. The airways in fatal asthma are occluded by tenacious plugs of exudate, mucus and cells. There is fragility of the airway surface epithelium and thickening of epithelial reticular basement membrane. Bronchial vessel dilation, congestion and oedema, an intense inflammatory cell infiltrate and enlargement of the mass of bronchial smooth muscle, and mucus-secreting gland each contribute to thickening of the airway wall. These changes contribute to the cardinal signs of inflammation (i.e. redness, heat, pain, swelling and secretion of mucus) and can profoundly modify the effects of airway contracture on airflow. The fragility and loss of surface epithelium, thickening of its underlying reticular layer and the presence of an inflammatory infiltrate, comprising activated T lymphocytes together with 'activated' and secreting eosinophils, are early events seen in biopsies of subjects with mild stable atopic asthma.

Adult↗

Differential expression of synaptic proteins in the frontal and temporal cortex of elderly subjects with mild cognitive impairment.

Alterations in synaptic protein stoichiometry may contribute to neocortical synaptic dysfunction in Alzheimer disease (AD). Whether perturbations in synaptic protein expression occur during the earliest stages of cognitive decline remain unclear. We examined protein levels of synaptophysin (SYP), synaptotagmin (SYT), and drebrin (DRB) in 5 neocortical regions (anterior cingulate, superior frontal, superior temporal, inferior parietal, and visual) of people clinically diagnosed with no cognitive impairment (NCI), mild cognitive impairment (MCI), mild/moderate AD, or severe AD. Normalized SYP levels were decreased approximately 35% in the superior temporal and inferior parietal cortex in severe AD compared with NCI. SYT levels were unchanged across clinical diagnosis in the cortical regions. Levels of DRB, a dendritic spine plasticity marker, were reduced approximately 40% to 60% in all cortical regions in AD compared with NCI. DRB protein was also reduced approximately 35% in the superior temporal cortex of MCI subjects, and DRB and SYP levels in the superior temporal cortex correlated with Mini-Mental State Examination and Braak scores. In contrast, DRB levels in the superior frontal cortex increased approximately 30% in MCI subjects. The differential changes in DRB expression in the frontal and temporal cortex in MCI suggest a disparity of dendritic plasticity within these regions that may contribute to the early impairment of temporal cortical functions subserving memory and language compared with the relative preservation of frontal cortical executive function during the initial stages of cognitive decline.

Aged↗

Distribution of 5-hydroxytryptamine and 5-hydroxyindoleacetic acid in human brain in relation to age, drug influence, agonal status and circadian variation.

The post-mortem brain concentrations of 5-hydroxytryptamine (5-HT) and 5-hydroxyindoleacetic acid (5-HIAA) were determined in 16 parts of the brain from patients with no history of neurologic, psychiatric or metabolic illness. The causes of death were either ischemic heart disease, infections disease, cancer or accidents. Forty-two men with a mean age of 57 years (range 18-95 years) and 19 women with a mean age of 62 years (range 23-79 years) were included. The influence of several factors were studied: brain weight, time between death and autopsy, storage time before chemical analysis, age, sex, agonal status, cerebral arteriosclerosis, cancer, opiate treatment and time of death during the day. Most correlations between the 5-HT concentrations in different brain parts were positive, the strongest correlations in the basal ganglia and the limbic system. No consistent pattern of age-related 5-HT changes were found. The females had significantly higher 5-HIAA concentrations in the cortex of the gyrus hippocampus. Final hypoxia seemed to decrease 5-HT concentrations. Opiate treatment reduced 5-HT and increased 5-HIAA concentrations. A marked circadian variation of 5-HT was found, most pronounced in the hypothalamus, the limbic system and some neocortical areas.

Adolescent↗