The stress response in the rat from harnessing for chronic intravenous infusion.
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Biomedical subjects
Publications and source records attributed to J R Border.
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The catabolism of glucose and amino acids has been studied in the normal, the fasted, and the fasted septic dog. The fasted septic dog oxidized more glucose and alanine, and had more gluconeogenesis from alanine and the five tritiated amino acids--glutamate, threonine, phenylalanine, leucine, and valine--as compared to the normal and equally fasted dog. Thus the total body protein catabolic state was characterized in biochemical terms. In contrast, following glucose infusion, the fasted septic animal responded much like the fasted animal in terms of decreased animo acid gluconeogenesis and decreased plasma concentrations of amino acids, fats and fat products, but considerably increased the oxidation of alanine. The increased alanine oxidation appeared to be primarily related to increased tissue clearance and increased plasma concentration. There was some suggestive evidence for enhanced oxidation of the tritiated amino acids including leucine and valine during glucose infusion. The protein catabolic state secondary to this sort of sepsis in dogs only on per os fluid support appears to be best characterized as a glucose catabolic state with alanine being oxidized directly. Such states are known to be ones of enhanced metabolic rate secondary to enhanced synthetic processes generally. This is probably related to enhanced sympathetic nervous system release of glucagon with insulin being normally responsive to glucose because of a normal plasma epinephrine.
Male rats received bilateral electrolytic lesions shortly after weaning in the ventromedial (VMN) and dorsomedial (DMN) hypothalamic nuclei, respectively. A third group of rats served as sham-operated controls. The animals were subjected to intragastric preloading with 33% d-glucose and egg-white solutions and a 33% corn-oil suspension, and ad libitum feeding was assessed hourly for the first 7 hr after preloading. The pattern of food-intake depression was similar in all groups but the quantitative greatest depression was found in the DMN rats. The response of these three groups of animals to a diet diluted with 20% alpha cell, a nonnutritive bulker, showed an initial failure to meter calories by both VMN and DMN rats which, however, was compensated for during the remainder of the 24-hr test period. In response to a 50% glucose-chow mixture, both VMN and DMN rats, as well as the controls, showed the same pattern and behaved like mature dynamic hyperphagic rats inasmuch as they did not eat more of this mix than of the standard diet. After a 48-hr fast, both VMN and DMN rats showed refeeding hypophagia rather than hyperphagia. The data suggest that Panksepp's contention that the VMN in the mature rat is involved in long-term satiety regulation may be extended to the weanling rat with VMN destruction. Thus, this controlling role appears established early in ontogeny.
Weanling male rats received electrolytic lesions in the ventromedial (VMN) and dorsomedial (MDN) hypothalamic nuclei, respectively. A third group served as sham-operated controls (CON). After the two hypothalamic syndromes had been well established, the animals were subjected to (1) a glucose preference test assessing the choice between a 10% w/v and a 35% w/v d-glucose solution, and (2) a test examining the anorexigenic effect of intraperitoneally injected glucose. Weanling rats with VMN lesions, like their mature counterparts, consistently preferred the stronger over the weaker glucose solution throughout the experiment (16 days). Weanling DMN rats, on the other hand, showed a bimodal response, initially like that of the CON rat, toward the end of the experiment, like that of the VMN rats. The weanling CON animals behaved differently from their mature counterparts, inasmuch as their preference for the dilute solution became evident only toward the latter part of the test. An analysis of the calorie intake shows that calories from glucose are similar in all three groups of rats, that the pattern and magnitude of caloric intake in DMN and CON rats are almost identical, and that the total caloric intake (from chow plus glucose) is reduced in the DMN rats because the calorie component from chow is profoundly reduced. In response to intraperitoneally injected glucose, VMN rats show a longer depression of food intake than has been reported for mature VMN rats. The CON and DMN rats recovered quicker and reached preinjection levels of food intake sooner than the VMN rats. The data indicate that in the weanling VMN rat, as in its mature counterpart, the VMN are involved in long-term feeding behavior and do respond to the metabolic signal arising from administered glucose. Nevertheless, the principle factor in their preference seems to be taste rather than solely a metabolic signal. The data show that the DMN are less involved in this sensing and integrating mechanism. In essence, the DMN rat functions quite normally, but its control system is set at a subnormal level.
Weanling rats received bilateral electrolytic lesions in the dorsomedial hypothalamus primarily destroying the dorsomedial hypothalamic nuclei (DMN). Sham-operated rats served as controls. After a 14 day postoperative period during which food intake (lab chow) and body weight were recorded, each of the above groups were subdivided into 2 groups. One DMN group and one sham-operated control group were continued on lab chow alone throughout the remainder of the study. The other DMN group and the second control group were given additional calories in the form of a liquid diet by stomach tube during 2 separate periods of 10 and 14 days, respectivly, to increase their caloric intake beyond that taken in spontaneously. Both tube-fed groups reduced their ad lib caloric intake from chow considerably and to the same extent. Body weight gains were similar in tube-fed versus non-tube-fed rats, whether with or without DMN lesions. After the second, 14-day-long tube feeding period, however, DMN rats regulated their body weight somewhat less precisely than the controls. This may be related to their reduced food intake during that time period. The data indicate that weanling rats with DMN lesions, despite their basic hypophagia, do not show a deficit in caloric metering and gross body weight regulation.
Serum electropherograms of trauma patients, when stained for glycoproteins, show striking changes in the alpha glycoproteins of these patients which revert to normal if and when they recover. Thus monitoring of the glycoprotidograms of trauma patients (contrary to ordinary protidograms) is likely to afford important information on the course of these patients' recovery. Of two glycoproteins that have been more closely studied, one, alpha1A acid glycoprotein, is a phagocytosis inhibitor; it is increased in the sera of trauma patients. The other, alpha2HS glycoprotein, is a phagocytosis promotor (or opsonin); it is decreased in the sera of trauma patients. Both the increase of the first and the decrease of the second glycoprotein may thus contribute to the known increased proneness to bacterial infection among these patients.
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Tissue carnitine levels have been measured in man and the dog. Skeletal muscle carnitine levels rise in the dog with starvation to roughly twice the normal level. An equal degree of starvation plus peritonitis is associated with unchanged skeletal muscle carnitine levels. In the presence of peritonitis, sequential skeletal muscle biopsies show a progressive fall in the tissue carnitine levels with a subsequent rise in those animals which survive and clear their peritonitis. Normal human skeletal muscle levels are essentially the same as in the dog. A combination of sepsis and starvation in man is associated with essentially unchanged skeletal muscle carnitine levels, whereas pure sepsis without starvation is associated with decreased skeletal muscle carnitine levels. It is suggested that these changes are in the direction expected for a limitation of fat catabolism and, in the presence of a limited exogenous source of glucose, that this would result secondarily in a protein catabolic state to supply glucose for the body's energy needs.
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