The role of citric acid in intermediate metabolism in animal tissues.
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Biomedical subjects
Publications and source records attributed to W A Johnson.
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The effects of diet-induced ketosis on the signs of hypoglycemia were investigated. Lard, medium chain triglycerides, or 1,3-butylene glycol comprised 43% of the diet fed to mice. The diet containing lard or medium chain triglycerides greatly protected the animals from the manifestations of acute insulin-induced hypoglycemia. Furthermore, both diets protected the animals from the effects of repeated insulin injections (every eight hours) for 10 days. In contrast, 1,3-butylene glycol had no protective effects. These experiments suggest that ketogenic diets may be of value in the treatment of recurrent hypoglycemic conditions.
Three days after ovariectomy adult female rabbits were injected intramuscularly with either 2 mug estradiol/kg b.w., 0.5 mg progesterone/kg b.w., 2 mug estradiol plus 0.5 mg progesterone/kg b.w., or oil vehicle daily for 5 days. On the sixth day the animals were anesthetized and given a continuous infusion of [14C]progesterone and [3H]5alpha-pregnane-3,20-dione (5alpha-DHP) for 4 h via the femoral vein. Head extractions, calculated from the difference in blood concentrations of radioactive steriods between the femoral artery and jugular vein, were in the range of 60-75% for both progesterone and 5alpha-DHP and were unaffected by the hormone treatments. Nine brain areas and the pituitary were analyzed for [14C]progesterone, [3H]5alpha-DHP and [14C]-5alpha-DHP. Generally, the brain and pituitary retention and distribution of [14C]progesterone and [3H]5alpha-DHP and the brain and pituitary metabolism of [14C]progesterone were unaffected by hormone treatments. In the cerebellum, progesterone treatment increased [14C]progesterone retention as compared to oil treatment. All tissues contained 2-7 times more [14C]progesterone than arterial blood concentrations. [3H]5alpha-DHP tissue: arterial blood concentrations ratios were much lower ranging from 0.9 to 1.78. [14C]progesterone and [3H]5alpha-DHP showed similar brain distribution with highest concentrations in the pons, pons reticulum and midbrain reticulum. All tissues converted progesterone to 5alpha-DHP, but only the cerebellum contained more [14C]5alpha-DHP than [14C]progesterone.
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The metabolic consequences of low-temperature kidney preservation were investigated. A comparison was made between kidneys which were immediately preserved and kidneys which had been ischemic for 1 hour. Two types of preservation techniques were used: (1) continuous perfusion with oxygenated plasma as described by Belzer and (2) a single flush with potassium-containing perfusate as suggested by Collins. Slices of renal cortex were removed at varying times during preservation and analyzed for a variety of metabolic intermediates. ATP levels were markedly reduced from normal. The Belzer technique was associated with higher ATP levels and ischemia lowered the ATP level. Kidneys perfused by the Belzer technique had lower ADP levels than those by the Collins method. Preservation caused marked elevation of tissue lactate, irrespective of ischemia or the technique used. We conclude that low temperature kidney preservation has profound effects on cellular metabolism. Therefore, the measurement of metabolic intermediates may provide a rational approach to the prediction of organ survival.
The end-organ response of any hormone is the result of many factors which precede the event, including biosynthesis, secretion, transport, distribution, and metabolism. These factors vary among different species. The metabolic clearance rate (MCR) of progesterone varies between 40 and 180 L./day/Kg. in man (60 to 70), monkey (40 to 50), rabbit (55 to 60), sheep (110), rat (120), and guinea pig (180). Major sites of clearance include liver, brain, and uterus. Specific metabolites of progesterone include 20 alpha-hydroxypregn-4-en-3-one (20 alphaOHP) and alpha-pregnan-3,20-dione (5 alpha-DPH). Liver, brain, and uterine clearances, extractions, and conversions of progesterone to these metabolites have been studied in various species under apparent steady-state conditions. A specific hormone action of progesterone, the appearance of uteroglobin in the rabbit uterus, has also been studied in varying horomonal states (estrogen, estrogen plus progesterone, and progesterone alone). These have all been used as examples of progesterone distribution and metabolism.
Neonatally and adult castrated male hamsters as well as neonatally androgenized and nonandrogenized female hamsters were tested for both mounting and lordosis behaviors during treatment with either testosterone or ovarian hormones. Neonatal androgenization facilitated mounting behavior in adult animals administered either testosterone or ovarian hormones and suppressed lordosis behavior in adult ovarian-hormone-treated animals. Early androgen effects on the display of lordosis behavior during adult testosterone treatment were complex and varied with the exact timing of perinatal endogenous or exogenous androgenization. Species differences in hormone-behavior relationships and the possible role of perinatal androgenization in the development of rodents' ability to aromatize androgens were discussed.
Four lines of quail; random-selected, male-selected, female-selected and male- and female-selected lines, were subjected to 37 plus or minus 1-6 degrees C from 3 to 5 weeks of age while another four lines, similarly selected, were reared at room temperature (15 to 27 degrees C). Selection for increased growth was practised for two generations using ten females and five males as parents in each line. A significant interaction between time and temperature was observed in the third generation progeny; when exposed to heat stress, the stress-adapted lines showing a superior growth rate. A sex X temperature interaction was also observed and was due largely to the control females being more sensitive to stress than the males. A cumulative realised heritability estimate of 0-47 plus or minus 0-15 for 5-week body weight was obtained.
Three random-bred lines of Japanese quail were crossed in a 3 X 3 diallel to estimate their combining ability for hatchability, growth rate, and age at 25, 50, 75 and 100% lay. The experiment was conducted as a randomized complete block design with a 3 X 3 X 2 X 2 factorial arrangement of treatments (3 lines of sire X 3 lines of dam X 2 ambient-temperature stresses X 2 sexes). Approximately 1200 eggs in three hatches were set; 496 progeny measured for five week body weight; and 212 hens observed for age at maturity. General combining ability effects were highly significant for percent hatchability. Specific combining ability was not important for hatchability in the three lines tested. Data on body weight revealed highly significant effects due to general combining ability, specific combining ability, sire X sex interaction, hatch, ambient-temperature stress and sex. Data for age at 25, 50, 75 and 100% lay indicated that general and specific combining abilities as well as maternal effects were all highly significant.
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