Enzyme activities of pyruvate carboxylase, phosphoenolpyruvate carboxykinase, pyruvate kinase and of mitochondria1 glycerolphosphate dehydrogenase were studied in the livers of rats under the following states of thyroid function : 1311-thyroidectomized rats, 1311-tl~yroidectomized rats treated with triiodothyronine, normal rats treated with excess of triiodothyronine, and normal untreated rats. I n the thyroidectomized group all of the enzyme activities listed were signilicantly diminished. After treatment with a single dose of triiodothyronine the activities of pyruvate carboxylase and of pyruvate kinase were restored to normal whereas phosphoenolpyruvate carboxykinase and-most markedly-glycerolphosphate dehydrogenase were raised above the normal level. After repeated administration of triiodothyronine to normal rats a further increase in the activity of pyruvate carboxylase, phosphoenolpyruvate carboxykinase and of glycerolphosphate dehydrogenase was observed.The activities of glycerolphosphate dehydrogenase and of pyruvate carboxylase 70 h following triiodothyronine injection into hypothyroid rats were more than 50 010 lower after treatment with actinomycin C suggesting that the increase in enzyme activities was due to increased synthesis of enzyme protein. Phosphoenolpyruvate carboxykinase activity was not changed significantly by actinomycin C.The possible significance of these thyroidihormone"*dependent enzyme fluctuations in controlling the overall rate of hepatic gluconeogenesis is discussed.There is evidence from the work of several groups
Summaryborn to healthy sows at known full term. All piglets were suckledPlasma volume and red cell mass of various organs in piglets aged 24 hr (n = 7) and 7 (n = 6). and 14 (n = 6) days were measured using eemTc-labeled albumin and "Cr-labeled red blood cells. Organ activities were counted in a whole-body counter. Blood volume and hematwrit were calculated. The blood volumes in $/g varied markedly between various organs. The lowest blood volumes at 24 hr of age were found in skin (21.9 + 5.0 pl/g), brain (33.3 ~t 8.4), and skeletal muscle (35.5 + 7.4). The highest values at this age were noted in liver (670.0 + 89.1), lung (533.8 f 80.7), spleen (332.0 + 82.8), and kidney (300.6 + 55.5). Blood volumes of about 150 pl/g were observed in heart muscle and thyroid gland and those of about 100 pl/g in thymus and gastrointestinal tract.The total blood volume was 100.2 * 3.9 pl/g at 24 hr and remained unchanged during the first 2 wk of life. A significant decrease in relative blood volume with growth was noted in liver and lung ( P c 0.01), and in skeleton ( P < 0.05). The blood volume, contained in the great vessels outside the organs, increased from 29.5 * 5.5% of total blood volume at 24 hr to 31.2 * 5.7% at 7 days and to 38.2 k 7.5% at 14 days of life. The total body/venous hematwrit ratio was about 0.84. Accordingly, tissue hematwrits of most organs were below the venous hematocrit. Only in spleen was the tissue/ venous hematwrit ratio (TH/VH) higher than 1.0. TH/VH of brain, gastrointestinal tract, thyroid gland, and thymus approached unity. The lowest TH/VH was found in kidney (0.54 f 0.08 at day 1). In skin, the TH/VH decreased from 0.98 * 0.10 to 0.82 * 0.07 during the first 2 wk of life.by their mothers. They were not treated 4 t i iron. The right atrium was cannulated with polyethylen catheters via the right external jugular vein for injection and withdrawal of blood. Each piglet received local analgesia with procaine at the site of catheterization, but no systemic drugs. Two ml of blood were withdrawn from the catheter and centrifu ed for 5 min at 1000 x g. The red R blood cells were labeled with chromium (17). Salt-poor human serum albumin (25%) was labeled by means of a commercial kit for electrolytic preparation of -technetium (New England Nuclear Corp., North Billerica, MA). Each preparation of *"Tclabeled albumin was carefully checked for particulate matter, turbidity, and pH (6). Labeling efficiency was determined with trichloracetic acid and membrane filtration (14). Batches containing more than 1% of unbound -Tc were discarded. One postmix blood sample of 1 ml was taken 10 min after injection of labeled red blood cells and 5 min after injection of labeled albumin. Previous equilibration studies have shown that mixing of red blood cells and of albumin are complete within that period (16). Loss of albumin from the intravascular space has been found negligible in this short time. The piglets were killed immediately after the labeling and blood collecting procedure by injection of 2 mval KC1 via the ca...
The agent 5-azacytidine, which directly affects nucleic acid metabolism, is a potent teratogen in NMRI mice. The establishment of general teratological data revealed clear-cut dose-response relationships after administration of this agent on either day 12 or day 14 of gestation. Inspection of skeletal abnormalities revealed a clear-cut phase specificity of this drug when administered on days 10 or 11 of pregnancy. Additional histological studies showed that central nervous system anomalies were induced mainly after administration of azacytidine on days 10, 11, 12, or 13 of pregnancy. A most conspicuous finding was the formation of anomalous glioblast islets within the ventricular zone covering the basal ganglia. The latter malformation mainly occurred after treatment on day 11 or 12 of pregnancy. Another important malformation syndrome was the appearance of capillary ectasias and hind paw hematomas, together with an intense necrotic cardiomyopathy after treatment on either day 11 or 12 of gestation.
Methylmercury chloride (MMC) was given to pregnant rats on the 6th, 7th, 8th, and 9th day after conception in doses of 0.05 and 2.0 mg/kg/day. The female offspring of these animals were tested 90 days after birth for learning ability using operant conditioning procedures. The rats were kept at 90% of their normal body weight and trained in a lever-box to press a bar in order to obtain a food pellet. Significant differences in the acquisition speed became apparent when the ratio of bar presses to reward was increased in a classical contingency of differential reinforcement of high rates even at MMC-doses of 4 X 0.05 mg/kg. These differences were not found in the general motility level nor in motor coordination.
Dextran (clinical grade, average mol. wt. 82,200) was labelled with 99mTc and the labelling efficiency was checked by paper and thin-layer chromatography and electrophoresis. The amount of free 99mTcO-4 was always less than 1%. The radiopharmaceutical was injected ID into the web space in hind legs of ten rabbits (200-600 microCi/0.05 ml). Scintigrams were taken at 10-min intervals up to 3 h in three rabbits. The injection site and the hind legs were massaged after injection in the other seven rabbits and scintigrams were taken at 10-min intervals up to 2 h. Blood samples were obtained at 5, 15, 30, 90 and 120 min in both groups. In addition a 180-min sample was also taken in the first group. At the end of the study the rabbits were killed and the popliteal lymph nodes and the organs were removed to be weighed and counted. Our results indicated a high concentration of radioactivity in the popliteal lymph nodes and massage at the injection site increased the average uptake of the popliteal lymph node from 1.12% +/- 0.77% to 4.28% +/- 1.57% at 3 and 2 h, respectively (P less than 0.001). In scintigrams the lymph channels and the nodes were very well visualised. The blood radioactivity levels were too low to present a background problem. With massage 30% of the injected dose was removed from the injection site in 2 h. We have shown that 99mTc-dextran is a good radiopharmaceutical for the visualisation of the lymph system and deserves further experimental and clinical studies.
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