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[The significance of topic differences and cadaveric changes of histamine and serotonin levels for the determination of the age of wounds in animal experiments (author's transl)].

Even when the extraction method of Fazekas for the determination of the so-called free histamine and serotonin is used, different dorsal skin areas of laboratory animals show certain differences in the amine content, which reach higher values for histamine than for 5-HT. 1) Related to the animal collective, no differences in the mean values of the 5-HT and histamine content between the right and left side of damaged dorsal skin of guinea pigs resulted, although in single cases remarkable differences (up to 1.26 microgram/g) were found. Descending from nuchal to caudal a decrease of the amine content--less in case of 5-HT, more in case of histamine--is noticed. The observed topical differences possibly depend on the continous moulting of the animals. 2) From these analytical data a method for statistical prediction is derived, which allows to state, when and with which probability a single difference value exceeds the normal variance. Applied to the comparative measurements wounded skin/control skin it is thus made possible to test the validity of the findings obtained in practical cases. 3) Postmortal changes of the amine content of the wounded as well as the normal skin are not detectable for the 5-HT, while in the case of histamine solely the values of the damaged skin first show a decrease (24 h p.m.), followed by an increase (48 h p.m., bacterial neogenesis?).

Animals↗

The effects of the method of death and lapsed time on proton relaxation time T1 in autopsied muscle samples.

RATIONALE AND OBJECTIVES: The variation of measured magnetic resonance T1 relaxation times of autopsied human muscle samples is confusing. Hence, the authors studied rats' muscles to evaluate the effect of fiber type, the relative area of nonmyofiber space, fat and water content, cell death, and the mechanism of death on proton T1. METHODS: Rats were studied on a 0.1 T magnetic resonance device. We studied how death by cervical dislocation, pentobarbital injection, or a combination of these methods, as well as the amount of time lapsed after death, variably affected T1. RESULTS: Death itself did not affect T1, but the mechanism of death did: rats killed by cervical dislocation after ether anesthesia had longer T1 than those killed with an overdose of pentobarbital. T1 was significantly shorter 1 day after death than at 4 hours after and returned to baseline levels within 4 days after death. Repeated warming caused variation in T1 and obscured other possible changes. CONCLUSIONS: Investigation methods should be strictly controlled and standardized before measurements of the relaxation time, T1, of muscle tissue will provide consistent results.

Animals↗

[Study on cerebral ATP level with bioluminescent: method to estimate the time of death].

This paper reported the changes of ATP content in dog's cerebral tissues during different time after death. ATP levels were determined by biolumi-nescent method. The results showed that ATP concentration decreased gradually along with prolonging of death time. The study has important value in estimating the time of death in forensic practice.

Adenosine Triphosphate↗

The biochemical changes in pericardial fluid after death. An investigation of the relationship between the time since death and the rise or fall in electrolyte and enzyme concentrations and their possible usefulness in determining the time of death.

This paper reports the biochemical changes that occur in pericardial fluid after death. Significant changes in relation to the time since death occurred in potassium, sodium, phosphate, protein and several commonly measured enzymes. The variation in individual results at similar times since death would limit the use of pericardial fluid biochemistry in determining the time of death.

Body Fluids↗

NMR relaxation behavior in living and ischemically damaged tissue.

A study by pulsed NMR techniques in living liver tissue has led to the discovery that the observed longitudinal relaxation decay behavior is strongly multicomponent. After death of the experimental animal, the relaxation decay curves evolve toward a single-component behavior. These changes can also be observed within a few minutes after the liver is excised and placed in a test tube, and they involve a high degree of quantitative and qualitative regularity and reproducibility. An excellent description of all observed NMR behavior is obtained from a dynamic two-compartment model. Rapidly relaxing volumes exchange water molecules with slowly relaxing volumes; associating only an increasing water molecule exchange rate with increasing ischemia accounts in quantitative detail for all observed changes. The exchange-rate values and their variation with tissue deterioration are in good agreement with that estimated for intra- to extracellular water exchange as limited by cell-membrane osmotic permeabilities. Possible applications of these results in different biomedical areas are discussed.

Animals↗

[Determination of death mechanisms in forensic-medical examination of a corpse].

Applied aspects of multivalued and modal logics served the basis for the proposed algorithm of tanatological analysis of autopsy material including formalization of semiquantitative data on changes in vital organs with further conversion of the estimated tanatogenetic coefficients in the form of probability suggestions leading to the conclusion about the kind and speed of tanatogenesis. The method is illustrated by cases from expert practice.

Adult↗

The state of preservation of the cadaver of the Marquise of Tai found in the Han Tomb No. 1 in Mawangtui near Changsha as revealed by the fine structure of the muscle and other tissues.

The cadaver in the Han Tomb No. 1 at Mawangtui near Changsha, Human Province, excavated during the Great Proletarian Cultural Revolution and the movement to criticize Lin Piao and Confucius, is the remains of the wife of Litsang, the Marquis of Tai, the Chancellor of the principality of Changsha in the early Western Han Dynasty. The cadaver, buried underground for more than 2,100 years, is very well-preserved. The results presented in this paper are a part of the multidisciplinary investigations of the state of preservation of the cadaver, which, together with the studies of the pathological changes and the cause of death, and the attempts at unveiling the secret of preservation, constituted the main objectives of the coordinated research activities for the Han cadaver. This paper describes the fine structure of the muscle and other tissues of the cadaver. By an extensive analysis of the electron micrographs of the psoas muscle, by fractionation of various fragments of the same, and by simulation experiments with fresh human muscle incubated with cathepsins, it is possible to show that the muscle fibril assumes the shape of a bamboo shoot and is made up of a stack of alternate layers of two "half A disks" (one wing of the A cylinder minus the H zone) to one Z disk, held together by remnants of the microfilaments and wrapped up in the sarcoplasmic reticulum. The H zone of the A band and the I filaments have preferentially autolyzed. The best preserved portions of the Han muscle still retain antigenicity to a certain extent. The best-preserved of all proteins is collagen, retaining much of the macromolecular, chemical and biochemical characteristics, whereas pancreatic enzymes, cytochrome C and other stable proteins could no longer be detected. The separation of degradative processes into endogenous autolysis and exogenous putrefaction, the synthesis of the factor of macromolecular stability and the factor of autolytic environment, and the disentanglement of the changes occurring soon after death and the long-term gradual changes, have been discussed in an attempt to understand how the corpse changed in the course of time and why it was so well-preserved. The well-preservedness of the cadaver of the Marquise of Tai once again testifies to the creative wisdom of the labouring class of our ancestors.

Cathepsins↗

Experimental selenium poisoning in Nubian goats.

The toxicity of sodium selenite was studied in 28 Nubian goats, 20 of which died or were killed in extremis 2 h to 21 d after dosing. Single or repeated daily oral doses of 160, 80, 40, 20 and 5 mg sodium selenite/kg were toxic to goats while daily doses of selenite ranging from 0.25 to 1 mg/kg/d for 225 d were not toxic to this species of animals. The main signs of poisoning were uneasiness, inappetence, dyspnea, salivation, diarhea, paresis of the hind limbs, arching of the back, and recumbency. The main lesions were hemorrhages in the rumen, reticulum, osmasum and abomasum, hemorrhagic or catarrhal abomasitis and enteritis, fatty change and necrosis of the centrilobular hepatocytes and of the cells of the renal convoluted tubules, splenic hemosiderosis, pulmonary congestion, haemorrhage, edema and emphysema, accumulation of lymphocytes in the vital organs, and straw-colored fluid in the serous cavities.

Animals↗

Coordinated expression of caspase 8, 3 and 7 mRNA in temporal cortex of Alzheimer disease: relationship to formic acid extractable abeta42 levels.

Recent studies support the hypothesis that Alzheimer disease (AD)-associated amyloid-beta protein (Abeta) may induce apoptosis mediated by a caspase cascade. To assess whether mRNA levels of caspase-3, 7, 8 and 9 change in AD brain, and whether these changes correlate with neurofibrillary tangles, Abeta40 or Abeta42 protein levels or senile plaques, 25 AD and 21 non-demented control brains were examined. Elevated mRNA levels of caspases-7 and 8 measured by a quantitative PCR method were observed in the AD temporal neocortex as compared to the control brains. No significant differences were noticed in levels of caspases-3 or 9 between AD and control brains. Multiple regression analysis demonstrated that, within subjects, the mRNA levels of caspase-8 strongly correlated with both caspse-3 and caspase-7 independently of postmortem interval. Further, there was a strong positive correlation of caspase-8 levels with formic acid extractable Abeta42 levels. Our results suggest that the transcriptional activation of key components of the apoptotic cascade correlates with accumulation of Abeta 42. Thus, a principal caspase pathway from caspase-8 to caspase-3 and/or 7 may contribute to neuron loss in AD brain.

Aged↗

Animal experience in the Günther Tulip retrievable inferior vena cava filter.

PURPOSE: To assess the retrievability of the Günther Tulip temporary inferior vena cava filter from a technical viewpoint, and consider the histopathologic changes that occur at the anchoring site of the filter prongs to the vein endothelium in Landrace pigs. METHODS: Twenty-two Günther Tulip retrievable filters were inserted in 22 experimental Landrace pigs via the jugular vein. Device implantation time was 0, 3, 7, 12, 14, 15, 16, 20, 30, 35 and 56 days. Study subjects were divided into two groups. In one group the filter was retrieved percutaneously via the jugular vein whereas in the other group it was removed surgically. The specimens obtained (vena cava and filter) were histopathologically examined. Prior to filter retrieval, a venacavography was obtained in all cases. Degree of retrieval difficulty was rated as follows: no difficulty (N), slight (S), mild (M), high (H) and unretrievable (U). RESULTS: Of the 22 implanted filters, 11 should have been removed percutaneously but this was impossible in three cases (U). In four cases the device was retrieved with no difficulty (N); in two cases the degree of difficulty was mild (M) and in other two it was high (H) and slight (S) respectively. Retrieval difficulties were observed after 16 days. Starting from day 20, there was evidence of fibrosis with thick intimal proliferation and total filter prong involvement, which accounts for the difficulty in retrieving the device. CONCLUSIONS: It is advisable not to exceed a filter retrieval time of 16 days in view of the fibrotic changes reported. It might be necessary to perform a larger study with more animals and with retrieval times between 14 and 20 days.

Animals↗

Postmortem endoscopy of the ocular fundus. A valuable tool in forensic postmortem practice.

Pathological changes of the ocular fundus in acute severe head or extracranial injury are difficult to document. In vivo examination usually has to be carried out under intensive care conditions. Postmortem ophthalmoscopy is usually impeded by rapid blurring of the cornea. Therefore, endoscopic fundal photography has been applied by using a pars plana approach during forensic postmortem procedures. This technique provides fundoscopic pictures of high quality as a valuable supplement for subsequent macro- and histopathological preparations and sections. Different patterns of fundoscopic findings seem to correspond to different types of injuries such as craniocerebral trauma, traumatic asphyxia and decompression sickness, and may allow some insight into the respective pathogenetic mechanism.

Adult↗

Differential expression of mitogen-activated protein kinases and immediate early genes fos and jun in thalamus in schizophrenia.

Despite a growing body of evidence demonstrating that mitogen-activated protein (MAP) kinase pathways play an important physiological role in the CNS, little is known about their role and function in various mental disorders including schizophrenia. Our previous studies have shown increased expression of several intermediates of the extracellular signal-regulated (ERK) cascade and downstream transcription targets in cerebellar vermis without any changes in mesopontine tegmentum and Brodmann's area 10 in patients with schizophrenia. Given the evidence for abnormalities in schizophrenia in a neural circuit involving the cerebellum and thalamus, the present study was conducted to examine the expression of MAP kinases extracellular signal-regulated kinase (ERK), c-Jun-N-terminal kinase (JNK) and p38, as well as immediate early genes fos (c-fos and fos B) and jun (c-jun, jun B and jun D) using a Western blot analysis and reverse transcription polymerase chain reaction (RT-PCR) in postmortem thalamus from schizophrenic and control subjects. There were significant increase in ERK2, c-fos and c-jun protein and mRNA levels in thalamus of patients with schizophrenia relative to controls. No statistically significant differences were found for ERK1, Fos B, Jun B or Jun D proteins in schizophrenic and control subjects. These results taken together with our previous findings provide new evidence for selective abnormalities of distinct MAP kinases and immediate early genes c-fos and c-jun in a circuit involving the thalamus and cerebellum, which may contribute significantly to the pathophysiology of schizophrenia.

Adult↗

A study on the vital reaction in wounded skin: simultaneous determination of histamine and polyamines in injured rat skin by high-performance liquid chromatography.

This paper describes a modified method of simultaneous quantitative determination of histamine and polyamines (putrescine, cadaverine, spermidine and spermine) in incised skin wounds of rats using high-performance liquid chromatography (HPLC) with a strong-cation exchange column, shim-pack ISC-05/S0504P, employing a linear gradient of 0.7-2.5 M sodium chloride. There was scarcely any change in the histamine content of the vital wounds throughout the one week experimental period, although content decreased slightly in 1-h-old wounds. On the other hand, concentrations of putrescine and spermidine increased suddenly 12 h after wounding, and spermine content increased slightly in 4-day-old wounds. There was no post-mortem change in the histamine, spermidine and spermine contents of vital wounds allowed to stand at 25 degrees C up to 24 h after death. Based on these results, this HPLC method may be useful for the determination of wound age during the period of healing.

Animals↗

pH Dependence of the progression in NMR T(2) relaxation times in post-mortem muscle.

Continuous NMR T(2) relaxation measurements were carried out on seven rabbit longissimus muscle samples in the period from 25 min to 28 h post-mortem at 200 MHz for (1)H. To display differences in post-mortem pH progress and extent of changes in water characteristics during conversion of muscle to meat, three of the seven animals were pre-slaughter injected with adrenaline (0.5 mg/kg live weight 4 h before sacrifice) to differentiate muscle glycogen stores at the time of slaughter. Distributed analysis of T(2) data displayed clear differences in the characteristics of the various transverse relaxation components dependent on progress in pH, as did the water-holding capacity of samples 24 h post-mortem. This reveals a pronounced effect of the progressive change in pH on the subsequent development in physical/chemical states of water during the conversion of muscle to meat. Finally, the relaxation characteristics are discussed in relation to supposed post-mortem processes of protein denaturation.

Animals↗

Culture and drug biotransformation capacity of adult human keratinocytes from post-mortem skin.

The aim of this study was to analyse viability, growth, differentiation and drug metabolic capacity of cultured human keratinocytes obtained from post-mortem skin. Epidermal cells were prepared from 1-day post-mortem paired sun-exposed (outer) and sun-protected (inner) sites of the upper arm, of donors aged 47-80 years. The percentage of viable cells obtained from post-mortem skin was only slightly lower than that usually obtained for keratinocytes isolated from fresh skin, and no alterations of epidermal markers were noted. Keratinocytes isolated post-mortem from non-exposed skin had a higher viability (78 versus 73%), and a more active proliferation, while their attachment rate, keratin composition, lipid synthesis capacity and transglutaminase activity levels were similar to those of epidermal cells obtained from the sun-exposed skin. Keratinocytes isolated from post-mortem skin expressed various phase I and II activities at levels similar to those obtained with keratinocytes isolated from fresh skin while drug metabolizing enzyme activities were consistently higher in sun-exposed compared to sun-protected cells. The results support the conclusion that skin collected post-mortem can represent an alternative source of viable and functional epidermal cells, and that the functional changes that occur in adult keratinocytes habitually exposed to the sun, affect much more strongly the drug metabolism capacity than the expression of differentiation markers.

Aged↗

Alterations of hHrd1 expression are related to hyperphosphorylated tau in the hippocampus in Alzheimer's disease.

The degradation of aberrantly phosphorylated tau in neurons plays an important role in the pathogenesis of Alzheimer's disease (AD). hHrd1 is a newly identified ubiquitin ligase involved in the endoplasmic reticulum (ER)-associated protein degradation. The expression and function of hHrd1 in AD brain remains elusive. In the present study, the expression of hHrd1 in AD hippocampus and the morphological relations between hHrd1 expression and pretangle formation were studied by using immunohistochemical single- and double-labeling methods. The results showed that hHrd1 was expressed in neurons and reactive astrocytes, especially in the CA2-CA4 hippocampal subfields. The ratio of hHrd1-positive neurons/astrocytes to total neurons/astrocytes was increased in the CA1 subfield in AD hippocampus compared with the age-matched controls (P < 0.05). Most Alz-50 labeled pretangles were colocalized with hHrd1, and the expression levels showed an inversed change, implied that hHrd1 might be associated with the degradation of hyperphosphorylated tau.

Aged↗

[Ultrastructural pathology of mechanical skeletal muscle damage].

In continuation of previous light microscope investigations the question has been raised whether the criteria determined for vital muscle damage using light microscopy, could be verified and perhaps extended for the ultrastructural region. In addition to existing human pathological material taken early post mortem, muscle tissue obtained from animal experiments was also examined. The evaluation concentrated on the muscle cells, the cell organelles and the contractile apparatus. An evaluation of semi-thin-sections was carried out in parallel. The following reaction patterns could be defined as vital reactions: hypercontraction bands, zones of rupture in narrow topological relationship to organelle changes, microstructure changes with disintegration of the fibre structure, subsarcolemmic and interfibrillary oedema, decomposition of the sarcolemma. The earliest vital reactions were detectable after only a few minutes survival time. The comparison between the results of animal experiments and human pathology and the application of the results to forensic pathology will be discussed.

Animals↗