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Biomedical subjects

G Hofecker

Publications and source records attributed to G Hofecker.

At least 55 records · Page 3Linked to original sources

Changes in pulmonary lipoprotein lipase activity in dogs following experimental bone fracture. A new concept on the pathogenesis of post-traumatic impairment of lung surfactant synthesis and accumulation of fat in lung vessels?

Five hours after a limited, nonhypotensive trauma without gross interference with coagulopathy, lungs of dogs were found to be completely deficient of heparin-releasable, metabolically active lipoprotein lipase. This indicates that the pathway of circulating lipoprotein triglyceride hydrolysis as a source of palmitate for pulmonary dipalmitoyllecithin synthesis is blocked post-traumatically. The possible significance of this finding on post-traumatic impairment of pulmonary surfactant synthesis and accumulation of fatty material in the pulmonary capillary bed is discussed.

Animals↗

[Specific incorporation of labelled tissue homogenates into the homologous organs of the rat (author's transl)].

The time course of the incorporation of radioactivity into the liver, kidney, heart, spleen, lung, adrenal glands, and testes following subcutaneous application of L-histidine-2,5-T-labelled homogenates of liver, kidney and heart has been measured in 105 male Sprague-Dawley rats aged 3 months (weight: x = 350 g). The homogenates had been prepared from organs of rats of the same age, sex and weight, each labelled with 400 muCi L-histidine-2,5-T. The maximal incorporation of activity from the homogenates into the organs investigated has been found 24 h after injection. In the kidney, however, an additional peak appeared already 5 h post applicationen. The comparison of the activities of the liver, kidney and heart, taking into account the differences in organ metabolism, revealed a significantly higher incorporation into the homologous than in the non-homologous organs. This specific incorporation appeared 2 h after the injection and could be found until about 24 h. The type of labelling, the method of sample preparation and the time of absorption allowed to conclude that the specific affinity to the homologous organs might have been due to a relatively small amount of short peptides. The functional significance especially for the regeneration of impaired organs has been discussed taking into account earlier results.

Animals↗

[Assessment of the biological age in the animal-experiment (author's transl)].

Experimental investigations of internal and external factors presumably influencing the aging process require an objective assessment of the biological age or vitality respectively by means of as many age parameters as possible. Using the rat, a valuable test animal in experimental gerontology, whose life expectancy of about 40 month allows longitudinal studies, a standard test programm for the estimation of the biological age has been developed. The age parameters used originate from investigations of 1. the tail tendon collagen, 2. the skin, 3. the aorta, 4. the ECG, 5. the lipofuscin content of brain and heart, 6. the tissue respiration of various organs, 7, the motor activity and 8. learning and memory. Using the above-mentioned age parameters a statistical measure for the biological age will be calculated by means of multivariate analysis and will allow the comparison of differeent age-and experimental-groups.

Aging↗

Models of the biological age of the rat. I. A factor model of age parameters.

The hypothesis of biological age postulates a fixed pattern in the aging of the multicellular organism. As a test of this hypothesis 23 age parameters of the rat were submitted to factor analysis. The data used in this study were a result of a long-term cohort study on 240 male Sprague-Dawley rats, which covered an age range of 10-30 months. The age parameters were obtained from various systems and levels of organization. The analysis revealed that there is a fixed pattern in the variations of the parameters. In this factor pattern the parameters are grouped into six factors, five of which can be attributed to the aging process. The first factor is interpreted as representing primary aging, factors 2-5 are interpreted as an expression of system-specific secondary processes of multicellular aging. Approximately 40% of the total variation of all parameters turned out to be random or due to processes other than aging.

Aging↗

Models of the biological age of the rat. II. Multiple regression models in the study on influencing aging.

The study of influences on multicellular aging requires mathematical models of biological age (BA) as a standard against which deviations from "normal aging" can be measured. A long-term cohort study with initially 1100 male Sprague-Dawley rats served to establish multiple regression models of BA and to test the effects of fast days, physical training, a combination of fast days plus physical training, and the long-term action of subcutaneously applied lyophilized heterologous fetal testis material. All influences started after the attainment of maturity. The models were calculated on the basis of an exponential decrease in vitality during senescence. Twenty-three parameters from a total number of 42 were selected for a general model. By means of a factor analysis, the general model was subdivided into five factor models of BA to distinguish between primary and various types of secondary aging changes. All experimental conditions showed clearly detectable but not dramatic effects on the general model of BA in the sense of a revitalizaion. The most pronounced effect was found in the group pretreated with testis lyophilisate. The results obtained with the factor models suggest that this effect might be due to influences on primary aging as well as on some secondary changes.

Aging↗

Assessment of modifications of the rate of aging in the rat.

Multivariate models of BA are, at present, the only way of measuring the main subject of gerontological research, namely, aging of the organism as a whole. Aging is obviously not a completely random process without any regularity, but shows a pattern which is determined by the organism's principles of order and its answer to the stochastic events of primary aging. Based on this theoretical concept, which is supported by results of factor analysis, multicellular aging may be described by a single complex variable, BA. However, the non-linearity of age changes and the different extent to which primary and secondary aging are involved, as well as factors other than aging, restrict the sensitivity of multiple regression models. Sensitivity may be increased by selecting parameters according to their discriminating power revealed by discriminant analysis. Wherever influences on aging are to be tested, a combination of the three types of multivariate methods will allow for an objectivation of effects and provide clues to a possible mode of action.

Journal Article↗

Age dependence of signal transduction and cell signaling as a major factor of intervention into the aging process.

Nowadays, it has become necessary to investigate the mechanisms underlying aging changes and their modulation. Of particular interest are the cellular and molecular level cell-cell and cell-matrix interactions. Thus, we partly determined in rats aged 9 and 31 months (a) the concentrations and the activities of signal molecules, such as G-proteins, cyclic adenosine monophosphate (cAMP) and kinases (cellular) and collagens, proteoglycans (PG) and fibronectin (extracellular) in vivo in the skin of the back, as well as in isolated fibroblasts and keratinocytes; (b) the cell proliferation and (c) we tried to retard the aging process in the skin by topical application (or by addition to cell cultures) of fetal mesenchymal cells, PGs, and soya matrix and we compared the above mentioned parameters with those obtained by stimulation of skin cells with growth factors. There are indications that there is (a) no change in the quantity of Gs-proteins but a reduction of the binding capacity. We found lower concentrations of cAMP, a reduced activity of protein kinase C in vivo, a higher collagen crosslinking, a lower PG concentration and no change of the amount of fibronectin in the old rat's skin and (b) there is a more or less extensive restoration of these parameters by all the above mentioned stimuli. So, we conclude that all the above mentioned influences modulate the aging process of the skin and its cells by intervention into the signaling pathways, by mediating new signals to the cells and hence by readjusting damaged feedforward systems in the cells.

Journal Article↗