摘要:

ExtractThe relation between changes in oxygen consumption (VO2) (in milliliters per kilogram and minute) and changes in levels of free fatty acids (FFA) and glycerol in plasma, lactate, pyruvate, and glucose levels in blood, and skin and rectal temperatures following norepinephrine or epinephrine infusions has been studied in neonatal piglets who lack brown fat and rapidly increase their body fat content after birth. Fourteen animals, age 17 hr-13 days (Table IA), each received two 25-min infusions of 2.0 μg/kg.min of norepinephrine (see Fig. 3); nicotinic acid (50 mg/kg) was administered prior to the second infusion. Five animals, age 5 hr-11 days (Table IB), each received two infusions of 0.2–4.0 μg/kg.min of epinephrine (Fig. 5).The elevated levels of glucose in blood, and FFA and glycerol concentrations in plasma observed following norepinephrine infusions correlated with postnatal age and body weight, suggesting that the magnitude of the norepinephrine-induced lipid mobilization was dependent upon body fat content. There was no definite tendency for VO2responses to norepinephrine to increase with increasing postnatal age (Table IA). The increases in glycerol levels (Fig. 2) and FFA (Fig. 1) concentrations occurring after norepinephrine stimulation were suppressible by nicotinic acid.The increases in VO2occurring after norepinephrine infusion (Table IA) were small (mean of 0.85 and 0.57 ml/kg.min during infusion prior to and following nicotinic acid administration, respectively) and variable and did not appear to be accentuated by previous starvation for 48 hr; they were related neither to elevations of any of the biochemical variables monitored nor to the small increases in skin and rectal temperatures observed. The changes in VO2after epinephrine infusions (Table IB) were quantitatively similar to those recorded during norepinephrine infusions and were not correlated to changes in concentrations of glucose, plasma FFA or glycerol (Fig. 5).SpeculationThe findings in the piglet, of small increases in VO2after norepinephrine infusion and the lack of a significant lowering of VO2response when norepinephrine challenge was preceded by nicotinic acid administration, contrast with those observed in adults of other species studied and preliminary results found in older piglets. It is therefore suggested that the newborn piglet has a relative inability to increase oxidation of norepi-nephrine-mobilized FFA and that this may improve with increasing postnatal age.

ISSN:0031-3998    

出版商:OVID    

年代:1971

数据来源: OVID

摘要:

ExtractSodium content and various components of sodium outflux were measured in erythro-cytes from 26 normal subjects, 25 patients with cystic fibrosis of the pancreas (CFP), and 20 parents of patients with CFP.Ouabain-insensitive, ethacrynic acid-sensitive fractional sodium outflux was diminished in erythrocytes from males with CFP (0.027versus0.051 for normal males) and from postpubertal females with CFP (0.012versus0.023 for normal adult females). This same component was normal in erythrocytes from prepubertal females with CFP (0.052versus0.046 for normal prepubertal females). Fractional sodium outflux in erythrocytes from obligate heterozygotes of either sex did not differ significantly from that of their normal counterparts.SpeculationNone of the components of sodium outflux reported here can be used as a genetic marker for CFP. The abnormalities of sodium outflux in patients with CFP are not related directly to the basic defect but instead represent a secondary feature of the disease.

ISSN:0031-3998    

出版商:OVID    

年代:1971

数据来源: OVID

摘要:

ExtractThe circulation was studied in 33 previable human fetuses (12–272 g) delivered by hysterotomy, while the placenta was still attached. The umbilical vein (UV) and in some instances umbilical or carotid artery (FA) were cannulated. Fetal and maternal pH, PO2, and PCO2were measured. Radionuclide-labeled microspheres (50 μ in diameter) were injected into the UV on one or more occasions from 1 to 36 min after delivery of the fetus. The distribution of the cardiac output (CO) was calculated from the relative amounts of radioactivity in each organ. In 11 fetuses, FA blood samples were withdrawn during microsphere injection, and CO and actual organ blood flows were measured.With advancing gestational age (10–20 weeks) there was an increase in total inferior vena caval return from 64 to 75% of CO. The proportion of CO to the placenta increased from 17 to 33% and to the gut from 5.5 to 9.2%. Superior vena caval return decreased from 32 to 23%, and the percentage of CO to the kidneys fell from 6.5 to 3.2%. In those fetuses in which repeated observations were made, there was a fairly uniform decrease in proportion of CO distributed to the placenta, probably owing to umbilical vessel constriction. This deterioration was not reflected by UV blood gases which in fact showed a decrease in PCO2and rise of PO2, when FA showed a rise of PCO2and fall in PO2and pH. Associated with the fall in FA pH there was an increase in the proportion of CO to the brain, myocardium, and adrenals. The proportion of CO to the brain increased significantly with increase of FA PCO2.SpeculationThe circulation of the previable human fetus may be studied at the time of hysterotomy. It is most important to realize that, even though umbilical venous blood gases may appear to reflect good physiological function, umbilical flow may be markedly decreased. This must be taken into account in all attempts to study placental function.

ISSN:0031-3998    

出版商:OVID    

年代:1971

数据来源: OVID

摘要:

ExtractTriodothyronine (T3) was given daily by injection to rats from 1 day of age to 2 hr prior to death. In the brain microsomal fraction of 5− to 6-day-old animals, incorporation of malonyl-CoA into total fatty acids increased from 0.9 to 2.25 mμmoles/mg protein. Although thyroid increased precursor incorporation into total fatty acids in other age groups, the difference was not statistically significant. Increased precursor incorporation was entirely due to increased formation of saturated fatty acids, and this effect was observed at all age groups.Incorporation of acetyl-CoA into saturated and unsaturated fatty acids by the mito-chondrial fraction was not increased significantly by administration of T3.In rats made hypothyroid at birth, fatty acid chain elongation was reduced in both the microsomal and the mitochondrial fractions. At 6 days of age, incorporation of malonyl-CoA by the microsomal fraction fell from 1.41 to 0.17 mμmoles/mg protein. These studies suggest that thyroid stimulates the microsomal-fatty acid-brain elongation system involved in the synthesis of saturated fatty acids characteristic of myelin lipids.SpeculationThe stimulation of fatty acid biosynthesis by thyroid hormone is specifically limited to the synthesis of saturated fatty acids by the microsomal fraction. Since the effect of thyroid is probably mediated by enzyme synthesis, we conclude that the microsomal fraction contains two distinct enzyme systems involved in fatty acid chain elongation, one for the formation of polyunsaturated fatty acids, the other for the formation of saturated fatty acids. The activity of the latter system increases at time of myelination, and as a consequence of thyroid stimulation.

ISSN:0031-3998    

出版商:OVID    

年代:1971

数据来源: OVID

摘要:

ExtractThe effect of epinephrine on the heart rate and arterial pressure of 138 chick embryos (2 days incubation age to hatching) and 2 chicks (1 day old) was studied. Twenty micrograms of epinephrine administered to embryos failed to produce a significant cardiac chronotropic response. In embryos of 2–2.5 days incubation age, epinephrine caused a pronounced fall in both systolic and diastolic pressure; no pressure change was seen during the second half of incubation day 3. In all older embryos there was a marked rise in both systolic and diastolic pressures with an increase in pulse pressure. These effects were most pronounced in 4− to 6-day-old embryos.SpeculationSystematic study of the effects of various autonomic drugs on the embryonic cardiovascular system may indicate when functional innervation occurs, and when and in which sequence α and β or other receptors make their appearance. It is conceivable that at certain stages of development only α or β receptors are present. If this is the case, then very young embryos in turn may provide unique subjects for the testing of newly developed autonomic drugs.

ISSN:0031-3998    

出版商:OVID    

年代:1971

数据来源: OVID

摘要:

ExtractA 7-year-old girl with periodic acidosis, lethargy, and coma beginning during the 1st year of life was studied. Episodes of ketoacidosis usually occurred with minor respiratory or gastrointestinal infections. There was history neither of peculiar body odor nor characteristic smell like that of sweaty feet. Hyperglycinemia, 4.2 mg/100 ml, and hyperglycinuria, 361 mg/liter, were found at times of illness with acidosis. A clinical diagnosis of ketotic hyperglycinemia was made in 1966. Glycine metabolism was therefore investigatedin vivousing14C-labeled glycine. The oxidation of glycine to respiratory CO2and formation of serine from glycine were found to be normal. The labeling of urinary hippurate, however, the largest component of the labeled products of glycine in the urine in normal individuals, was virtually zero. An abnormal, labeled product of glycine was found in the urine and identified as isovalerylglycine. As much as 6% of the14C-glycine administered was incorporated into urinary isovalerylglycine within 24 hr. Isovalerylglycine in urine was 2880 mg/24 hr, while normal individuals excrete less than 2 mg/24 hr. Isovaleric acid was found in both urine and plasma. Isovaleric acid in the plasma and urine, 2.86 mg/liter and 2.56 mg/day, respectively, was only five to six times larger than that found in normal individuals. Formation and excretion of isovalerylglycine may be a compensatory mechanism for the elimination of toxic amounts of isovaleric acid from the body. Biosynthesis of such huge amounts of isovalerylglycine may alter the overall metabolism of glycine. Isovaleric acidemia may present with hyperglycinemia and hyperglycinuria. Examination of the urine for isovalerylglycine is a convenient method for detecting the syndrome of isovaleric acidemia.SpeculationIsovaleric acidemia, in common with propionic acidemia with ketotic hyperglycinemia and methylmalonic acidemia, produces dramatic episodes of ketoacidosis. It is now clear that, like these conditions, isovaleric acidemia can also produce leukopenia and elevated concentrations of glycine in body fluids. The mechanisms causing these abnormalities are unknown. Elucidation of metabolic interfaces among these conditions could lead to understanding of the pathophysiology involved.

ISSN:0031-3998    

出版商:OVID    

年代:1971

数据来源: OVID

摘要:

ExtractThe cellular and humoral components of the chemotactic response in neonates have been compared with those in adults.Leukocytes from neonates were compared with those from adults in their ability to movetoward chemotactic factors (CF) generated from pooled, normal serum. Neonatal leukocytes showed a consistent and highly significant deficiency in their response to chemotactic factor generated fromStaphylococcus aureus, Escherichia coli, or albumin-antialbumin (Table I).Chemotactic factor generated from neonatal and adult sera was compared for its ability to stimulate migration of a standardized, normal leukocyte pool. A small but highly significant difference was seen between the amounts of effective CF generated from neonatal sera and that from adult sera. The difference was found with all three generating agents (Table II).The mechanism by which leukocytes undergo chemotactic migration is presently unclear. It is possible that in neonates cellular defects in leukocyte phagocytosis and leukotactic chemotaxis may be related to developmental immaturity of common biologic mechanisms.Although other serum factors may be involved, it appears that the separate deficiencies of neonatal sera in generation of CF and enhancement of phagocytosis may both be related to deficiencies of C3 and C5.The enhanced susceptibility to infection in neonates cannot be explained simply by a selective deficiency of IgM. Addition of IgM failed to correct the humoral deficiencies of chemotaxis and phagocytosisin vitro. Further, a deficiency of IgM would not explain the cellular deficiencies demonstrated. It is only by a sequential analysis of the entire inflammatory response in the neonate that these relations will become clear.SpeculationIt has become apparent that the relative susceptibility of the neonate to bacterial infections is the result of a number of deficiencies involving bothhumoralandcellularaspects of the neonatal inflammatory response. The future delineation of these individual defects may lead to improved therapeutic approaches in neonatal septicemia and, also, provide valuable information on the mechanisms involved in the normal inflammatory response.

ISSN:0031-3998    

出版商:OVID    

年代:1971

数据来源: OVID

摘要:

ExtractThe fetal hemoglobin (Hb-F) of blood samples from 11 newborn babies (two normal infants, two sickle cell trait carriers, two Hb-C heterozygotes, two infants with Hb-SG disease, one infant with Hb-Richmond heterozygosity, one β-thalassemia heterozy-gote, and one infant with a heterozygosity for the hereditary persistence of fetal hemoglobin) and from 16 adults (eight normals, two Hb-S heterozygotes, one Hb-C heterozygote, and five SC patients) has been examined to determine the ratio of the two structurally different γ chains, namely theGγ andAγ chains. This ratio is about 2:3 in the Hb-F of the adults and, therefore, significantly different from the 3:1 ratio in the Hb-F of the newborn. This newborn ratio undergoes a considerable change between the 3rd and 4th months of life, at which time it approaches that of the Hb-F of adults.SpeculationThe mechanism by which the gradual change from γ chain synthesis to β and δ chain synthesis is controlled remains unclear. However, the change in the ratio of production of structurally different γ chains as a function of postnatal age indicates a rather complex mechanism which probably involves an unequal repression of the γ chain structural genes. Any explanation of the mechanism must take into account the fact that the production of two genes, theGγ andAγ, is greatly decreased, whereas that of two other genes, the β and δ, is started. Perhaps a closely related or even identical mechanism controls not only the ratio of production of theGγ andAγ genes but also that of the β and δ genes.

ISSN:0031-3998    

出版商:OVID    

年代:1971

数据来源: OVID