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Possible markers for postmortem drug redistribution.

The possibility that postmortem biochemical changes in blood might parallel drug redistribution and thus serve as markers was explored in a detailed case study. Eighteen blood and 14 tissue and fluid samples were taken at autopsy 16 h after the death of a 34-year-old female from amitriptyline overdose. Ranges of drug concentrations in blood were amitriptyline 1.8 to 20.2 micrograms/mL, nortriptyline 0.6 to 7.3 micrograms/mL, levels were lowest in femoral vein and highest in pulmonary vein blood. Corresponding levels of 17 amino acids showed markedly different patterns of site-to-site variability. There was a strong positive correlation between individual amino acid and drug concentrations in pulmonary blood samples (n = 5), particularly for glycine, leucine, methionine, serine, and valine. In blood samples from the great veins and right heart (n = 10), the correlation was less strong (r = 0.6 to 0.7). Methionine showed a strong positive correlation in pulmonary samples (r = 0.93), and negative correlation in great veing samples (r = -0.68). Lactic acid showed a strong negative correlation in pulmonary samples (r = -0.93) but a positive correlation in great vein samples (r = 0.71). Alanine aminotransferase, alkaline phosphatase, aspartate aminotransferase, gamma-glutamyl transferase, glucose, and bilirubin had a weak positive correlation with drug levels in great vein samples but not pulmonary samples. The results suggest that hepatic enzymes are relatively poor markers for postmortem hepatic drug shifts but that amino acids, particularly methionine, may be useful markers for pulmonary drug shifts.

Adult↗

[Microscopic myocardial changes and their significance for forensic medical diagnosis].

Morphological myocardial changes essential for diagnosis in forensic medical medicine are listed as well as alterations in the vessels of the myocardium, cardiac muscular fibers and cardiomyocytes important for diagnosis of death of ischemic heart disease, acute alcohol poisoning, alcohol cardiomyopathy, closed cardiac lesions. Changes induced by reflex impacts on the heart and postmortem alterations are also shown.

Cardiomyopathies↗

[Quantitative characteristics of blood redistribution after death by radioactive indication].

The methods of radioactive detection and external radiometry were used to study the distribution of blood in cats and rats during 24 hours after heart arrest. Labeled albumins (131I) and erythrocytes (51Cr) were used as blood indicators. The animals after death were stored in a horizontal or, in some tests, in vertical position at room temperature. The activity was measured in the horizontal and sagittal planes in strictly defined sites (30 altogether) or by scanning of the entire body within 3-5 min after circulation arrest as well as at 5 and 24 hours. No significant changes in distribution of plasma and erythrocytes during 24 hours postmortem in the horizontal position were shown to occur, while in the vertical position there was an insignificant increase of the blood content in the lower part of the body.

Animals↗

Discrimination of recent ischemic myocardial changes in WHHLMI rabbits from the findings of postmortem degeneration.

To distinguish recent ischemic myocardial changes in myocardial infarction-prone Watanabe heritable hyperlipidemic (WHHLMI) rabbits from general postmortem myocardial degeneration, we examined hearts of WHHLMI rabbits after sudden death and postmortem hearts of non-atherogenic rabbits. Hearts of 8 WHHLMI rabbits were excised within 30 min of sudden death and hearts of 27 non-atherosclerotic rabbits were excised at designated periods after sacrifice. A large number of myocardial cells from WHHLMI rabbits exhibited features characteristic of ischemia (intercellular gap, intracellular edema, eosinophilia, disappearance of myocardial cells, indistinct nuclei, wavy myocardial fibers) simultaneously at regions close to proximal occluded coronary arteries. Although postmortem hearts of non-atherosclerotic rabbits exhibited similar characteristics, several features characteristic of autolyzed myocytes were also randomly observed in the left ventricle wall. Each feature was detected independently in myocardial cells or regions of the ventricle wall. In conclusion, we found several unique characteristics associated with myocardial infarction which enable discrimination between recent ischemic myocardial changes and myocardial degeneration following death.

Animals↗

Mapping changes in the human cortex throughout the span of life.

In this review, the authors summarize the literature on brain morphological changes that occur throughout the human life span from childhood into old age. They examine changes observed postmortem and in vivo where various brain MRI analytic methods have been applied. They evaluate brain changes observed with volumetric image analytic methods and voxel-based morphometric methods that may be used to better localize where changes occur. The primary focus of the review is on recent studies using state-of-the-art cortical pattern-matching techniques to assess age-related changes in cortical asymmetries, gray matter distribution, and brain growth across various age spans. The authors attempt to integrate findings from the in vivo studies with results from postmortem studies and analyze the complicated question of when brain maturation stops and brain aging begins. Analyzing the regional patterns of change initiated at various ages may help elucidate relationships between changing brain morphology and changing cognitive functions that occur throughout life. Long-range longitudinal studies, correlations between imaging and postmortem data, and more advanced image acquisition and analysis technologies will be needed to fully interpret brain morphological changes observed in vivo in relation to development and aging.

Adolescent↗

[Hypostasis-induced changes in the breast area].

When the anterior thoracic wall is within the hypostatic area, postmortem lividity in the region of the nipples and their immediate vicinity is less intense or absent. Where hypostatic skin haemorrhages (so-called vibices) are present, these are also found outside the areola of the nipple only. This phenomenon is visible not only externally, but is particularly pronounced on the cut surface. A possible explanation may be the different distribution pattern of connective tissue, smooth muscles and blood vessels inside and outside the areola mammae. Based on 13 cases from the forensic autopsy material--mostly drug related deaths--the macromorphological findings and their histological correlates are presented.

Adult↗

Bone changes of mucolipidosis II at different ages. Postmortem study of three cases.

Bone changes are a constant feature of mucolipidosis II, with striking differences between newborns and older children. Intracellular, membrane-bound vacuoles were found in the chondrocytes, osteoblasts, osteocytes, and stromal fibroblasts of three affected children. Osteoclasts and marrow cells were unaffected. Ricketslike lesions were present at birth in the two younger cases, whereas signs of high bone turnover and defective calcification were no longer present in the older child. Severe abnormalities of the metaphyseal plate with the loss of normal cartilage architecture and the absence of endochondral ossification were the major changes in this age group.

Age Factors↗

[Ultrastructural study on the nucleus pulposus of the inter-vertebral disc--the behavior of the cells in the nucleus pulposus and their autolytic changes in the monkey].

Ultrastructural studies were carried out to examine the normal structure and postmortem autolytic changes of the cells and matrix of nucleus pulposus using adult monkey. Two kinds of cells were observed in the nucleus pulposus. The one was chondrocyte, which contained normal organelles and that was characterized by large halo. The halo was composed of numerous "crista like structures", that were regarded to form the matrix of nucleus pulposus. The other was notochordal cell, most of which appeared in grouping or separately, and yet had cell activity. In addition, there were the intermediate type of cells between chondrocyte and notochordal cell. The ultrastructural autolytic changes were rarely seen in the cells of 6 hours after death, but the changes in the halo and in the cytoplasm were remarkable after more than 12 hours. The autopsied nucleus pulposus for electron microscopical examination should be used within 6 hours after death in usual room temperature.

Animals↗

Scanning electron microscopy of the human cochlea--postmortem autolysis artefacts.

Changes in the ultrastructure of the cochlea due to postmortem autolysis make the assessment of the normal or damaged anatomy difficult. Three methods of preserving the human cochlea were compared on the basis of the state of preservation of the sensory cell hairs of the organ of Corti as seen in the scanning electron microscope. Perfusion of the perilymphatic space with a glutaraldehyde-formaldehyde fixative within 40 min of death gave preservation as good as that seen in animal studies. Injecting formalin into the middle ear within 40 min of death allowed artefacts to develop when compared with the control ear which had been perfused with fixative. Refrigeration and early removal of the temporal bone gave poor preservation of surface structures.

Autolysis↗

Overlapping regional distribution of CCK and TPPII mRNAs in Cynomolgus monkey brain and correlated levels in human cerebral cortex (BA 10).

UNLABELLED: Tripeptidyl peptidase II (TPPII) is a high molecular weight exopeptidase important in inactivating extracellular cholecystokinin (CCK). Our aims were to study the anatomical localization of TPPII and CCK mRNA in the Cynomolgus monkey brain as a basis for a possible functional anatomical connection between enzyme (TPPII) and substrate (CCK) and examine if indications of changes in substrate availability in the human brain might be reflected in changes of levels of TPPII mRNA. METHODS: mRNA in situ hybridization on postmortem brain from patients having had a schizophrenia diagnosis as compared to controls and on monkey and rat brain slices. RESULTS: overlapping distribution patterns of mRNAs for TPPII and CCK in rat and monkey. High amounts of TPPII mRNA are seen in the neocortex, especially in the frontal region and the hippocampus. TPPII mRNA is also present in the basal ganglia and cerebellum where CCK immunoreactivity and/or CCK B receptors have been found in earlier studies, suggesting presence of CCK-ergic afferents from other brain regions. Levels of mRNAs for CCK and TPPII show a positive correlation in postmortem human cerebral cortex Brodmann area (BA) 10. TPPII mRNA might be affected following schizophrenia. DISCUSSION: overall TPPII and CCK mRNA show a similar distribution in rat and monkey brain, confirming and extending earlier studies in rodents. In addition, correlated levels of TPPII and CCK mRNA in human BA 10 corroborate a functional link between CCK and TPPII in the human brain.

Aminopeptidases↗

Effect of sire on mu- and m-calpain activity and rate of tenderization as indicated by myofibril fragmentation indices of steaks from Brahman cattle.

The objectives of this study were to assess the influence of sire on mu- and m-calpain activities, to evaluate the relationships of activities of these enzymes to other traits related to beef palatability, and to assess the influence of sire on the rate of tenderization (as measured by myofibril fragmentation index [MFI]) in Brahman longissimus muscle. Brahman calves (n = 87), sired by nine bulls, were born, weaned, fed, and slaughtered in central Florida. Traits evaluated were mu- and m-calpain activities and MFI after 1, 7, 14, and 21 d of aging. Other traits were analyzed to determine their associations with mu- and m-calpain activity and MFI, including calpastatin activity, percentage of raw and cooked lipids, Warner-Bratzler shear force (WBSF) values after 7, 14, and 21 d of aging, and sensory panel rating of tenderness, juiciness, and connective tissue amount after 14 d of aging. Data were analyzed using a model with sire, sex, year, and slaughter group (calves of the same sex slaughtered on the same date) as fixed effects, and adjusted to a constant adjusted 12th-rib fat thickness. Sire affected mu-calpain activity (P < 0.04), calpastatin activity (P < 0.01), d-14 MFI (P < 0.02), d-7 WBSF (P < 0.05), d-14 WBSF (P < 0.04), and sensory panel juiciness score (P < 0.01), but not (P < 0.75) m-calpain activity. Measures of tenderness and palatability were generally moderately to strongly correlated (both simple and residual correlations) with calpastatin and m-calpain activity. Myofibril fragmentation index residuals (adjusted for all model components except sire) after all aging periods were fitted using nonlinear regression to the exponential curve (MFI(i) = kappa0 + kappa1 exp[kappa2 t(i)] + epsilon(i), where t(i) represents aging in days, k0 is ultimate MFI after aging, kappa1 is the difference between initial and ultimate MFI, kappa2 is the rate of increase in MFI, and epsilon(i) is the error term associated with the ith observation, assumed to be independent and identically distributed normally). Sires had different estimates and combinations of estimates, which were used to plot MFI change with time. These curves visually differed for sires and suggested that postmortem tenderization extent and rate differ as well. Use of a combination of these estimated parameters in a selection/carcass sorting program represents an alternative consideration for tenderization improvement programs.

Animals↗

Morphological changes of rats muscles at various postmortem intervals by scanning electron microscopy.

The aim of this study was to observe the morphological changes of muscle in the process of rigor mortis. The quadriceps of 40 rats at various postmortem intervals were observed under the scanning electron microscope (SEM) and the light microscope by phosphotungstic acid-haematoxylin (PTAH) stain. The results showed that the striations of muscle were blurred within 4 h, but they became apparent from 6 h to 24 h after death. The authors suggest that this phenomenon be associated with the increased resistance of muscle against the postmortal changes. The observations by scanning electron microscopy and light microscopy have revealed that the muscles do contract in the process of rigor mortis because the distance between two Z lines shortens and the 1 band narrows, compared with those in anaesthetised animals. The basic biochemical process for the formation of rigor mortis is the same as that of muscle contraction except that the former happens postmortem and the latter antemortem.

Animals↗