摘要:

SummaryThe present study was designed to investigate some of the possible factors responsible for the low rate of the oxidative use of glucose observed in neonatal rat brain.An evaluation of the role of pyruvate dehydrogenase (PDH, EC 1.2.4.1) showed that at all stages of brain development, the activities of both molecular forms of this enzyme are considerably less than those reported for the enzymes localized above in the glycolytic pathway. The proportion of both molecular forms is not altered during brain maturation. The activities of the active form and of the total enzyme in adult brain are 0.56 and 1.1 μmole/min/g brain, respectively. It is concluded that PDH represents the rate-limiting step in the oxidation of glucose by neonatal brain due to a delay in the synthesis of the enzyme protein.A “cross-over” plot of glycolytic intermediates in neonatal brain showed that only fructose 1,6-bisphosphate concentrations are significantly lower than in adult brain, indicating a block at the level of phosphofructokinase (PFK, EC 2.7.1.11). A marked increase in citrate concentrations in neonatal brain (values ranging from 0.44–0.82 μmole/g brain) with regard to adult levels (0.28 μmol/g brain) is suggested to be responsible for the inhibition of the enzyme.Glucose 6-phosphate concentrations in neonatal brain are not different from adult values. Despite increasing ketonemia neither consistent intracerebral accumulation of glucose nor a decrease in the brain/blood ratio of glucose is observed during brain maturation. These data argue against limitations of glucose use at the level of hexokinase or membrane transport in the neonatal brain.SpeculationKetone bodies are major substrates of the neonatal brain in that they fulfill to a large extent both the energy requirements of the brain and provide carbon for the needs of biosynthetic processes. The dual function of ketone bodies cannot be substituted for alternatively by glucose due to a limitation in the oxidative breakdown of glucose observed in young rat brain. Thus, glucose is saved for preferential use in the pentosephosphate pathway, providing hydrogen equivalents for the synthesis of myelin lipids, a process which is very active in neonatal brain.

ISSN:0031-3998    

出版商:OVID    

年代:1979

数据来源: OVID

摘要:

SummaryInitial observations in adults revealed that peripheral neuropathy, as documented by reduced conduction velocity is common L chronic renal failure. Critical analysis of this problem in children on long-term dialysis is scarce, consisting of a single report which demonstrated that the motor nerve conduction velocities were decreased early and frequently with more severe depression in peroneal nerve velocities. This is in distinct contrast to data from adults, in whom uniform rates of deterioration are encountered. In addition, a direct correlation of the degree of nerve conduction defect with the severity of the renal failure is found in adult patients.The present study showed a relative lack of nerve conduction defects in 11 children on long-term hemodialysis. With rare exceptions, the conduction velocities were normal. To date, no clinical symptoms of neuropathy were evident in our patients. It would seem that, with the short-dialysis schedule of 12–14 h/wk over a period of up to 5 yr, there is no progressive neuropathy as quantitated by nerve conduction measurements.SpeculationNutritional augmentation, treatment with 1,25-vitamin D3, suppression of parathormone and other as yet undefined age-specific factors may be responsible for the prevention of peripheral neuropathy in these children, as compared to the high incidence in adults receiving similar dialysis treatment.

ISSN:0031-3998    

出版商:OVID    

年代:1979

数据来源: OVID

摘要:

SummaryPersistent endogenous hepatic glucose production is characteristic of the newborn lamb in response to exogenous glucose infusion. The hypothesis that decreased hepatic sensitivity for insulin may be a major mechanism accounting for the imprecision in glucose homeostasis was tested in 28 unanesthetized, mixed breed, term lambs. Either 0, 5.7, 6.2, or 12.5 mg glucose/kg/min was infused for a period of 2 hr after which simultaneous infusion of 0, 1.25, or 6.25 mU porcine insulin/kg/min was administered for 4 hr to produce a euglycemic, hyperinsulinemic steady state. Gluconeogenesis from lactate was measured by determining the ratio of14C to3H in plasma glucose during the simultaneous infusion of14Cu-lactate and3H6-glucose. Endogenous hepatic glucose production was determined by the prime-constant infusion technique of Steele using3H6radio-labeled glucose during a 50-min turnover period after the infusions. All animals maintained a constant plasma glucose concentration and glucose specific activity during the turnover period. Gluconeogenesis was significantly suppressed when insulin levels were in the 49–61 μU/ml range although endogenous glucose production was not affected. When plasma insulin concentrations were above 200 μU/ml, both gluconeogenesis and endogenous glucose production were significantly suppressed. These changes were observed irrespective of the steady state blood glucose concentration. Plasma glucagon concentrations were the same in all experimental groups and were not affected by glucose and insulin infusion nor were they responsive to differences in plasma glucose or insulin concentrations. Our data indicates that insulin may be the major hormone for the control of glucose homeostasis in the neonatal lamb and that there is a quantitative difference in the response of the various glucose homeostatic mechanisms to insulin.SpeculationRegardless of the plasma glucose concentration and the resultant counter-regulatory responses that may occur during prolonged continuous glucose infusion, endogenous glucose production in the neonatal lamb may be primarily controlled by insulin.

ISSN:0031-3998    

出版商:OVID    

年代:1979

数据来源: OVID

摘要:

SummaryThe lungs of intrauterine 135–136-day-old lambs were lavaged with amnionic fluid, with or without meconium, to determine the effect on lung phosphatidylcholine (PC) concentration, synthesis, and function. No differences were apparent between animals lavaged with amnionic fluid or amnionic fluid with meconium. When lavaged lungs were compared to nonlavaged controls, no detectable differences were observed in histology or the quantity of saturated (SPC) and unsaturated phosphatidylcholine (UPC). However, the lavaged lungs retained a larger fraction of maximal lung volume at 5 cm H2O distending pressure and the incorporation of (32P) orthophosphate into lung PC was significantly reduced. In addition, two lavaged animals who became acidotic (pH < 7.20) exhibited decreased incorporation of (14C) palmitate into whole lung unsaturated, and saturated phosphatidylcholine.SpeculationThese data indicate that amnionic fluid can reduce lamb lung de novo synthesis of PC and may contribute to the alterations in lung PC found in neonatal syndromes of respiratory distress. Acidosis may accentuate this effect.

ISSN:0031-3998    

出版商:OVID    

年代:1979

数据来源: OVID

摘要:

SummarySix newborn lambs were studied during continuous infusion of saralasin acetate, 5 μg/kg/min for 135 min; 40 min after beginning saralasin, furosemide (2 mg/kg) was injected over 1–2 min. In addition, six anephric lambs were studied after injection of furosemide. Plasma renin activity (PRA) increased from 23 ± 2.7 ng/ml/hr (M and SE) to 85.8 ± 16.5 (P< 0.05) during infusion of saralasin alone and remained at this level after injection of furosemide. PRA did not increase above base line after injection of furosemide in the anephric lambs. Blood pressure dropped after saralasin infusion in the normal lambs (P< 0.05), and after furosemide injection (P< 0.05) in both groups. Plasma aldosterone concentrations did not increase in response to furosemide in either group. The results suggest that angiotensin II is important in maintaining blood pressure in the newborn and exerts antagonistic effects on the renal renin secretion mechanism.SpeculationThe renin-angiotensin-aldosterone system is activated in the normal newborn. Possible reasons for the activation include decreased circumferential tension of small arteries and salt wasting.

ISSN:0031-3998    

出版商:OVID    

年代:1979

数据来源: OVID

摘要:

SummaryExperiments were performed on 11 long-term fetal lamb preparations (103–138 days of gestation) to investigate the sensitivity and relative responsiveness of the fetal volume receptors in modulating fetal plasma arginine vasopressin (pAVP) secretion and plasma renin activity (PRA) secretion during fetal hypovolemia and after fetal blood volume replacement. During fetal hemorrhage there were significant decreases (P< 0.05) in fetal hematocrit (34.7 ± 2.58 to 27.0 ± 1.64%), plasma proteins (3.14 ± 0.15 to 2.78 ± 0.19 g/100 ml), mean arterial blood pressure (MABP) (58.1 ± 2.59 to 52.2 ± 2.60 mmHg) and fetal arterial pH (7.38 ± 0.01 to 7.35 ± 0.01). A significant increase in fetal pAVP concentration from 0.73 ± 0.21 to 34.9 ± 10.04 μU/ml (P< 0.01) and fetal PRA from 4.78 ± 2.22 to 40.4 ± 18.31 ng/ml/hr (P< 0.05) was demonstrated at the peak of fetal hemorrhage. Two hr after correction of the fetoplacental blood volume, these values were back to base line levels. No change in either maternal pAVP or PRA was seen during fetal hemorrhage. When individual values for log pAVP and log PRA were plotted as a function of percent of fetoplacental blood volume removed the correlation coefficients were 0.82 and 0.60, respectively. A multiple regression analysis showed a high correlation of log pAVP and log PRA with the volume of blood removed and a low partial correlation with the fetal MABP. This suggests the decrease in fetal MABP was not the primary factor explaining the increase in pAVP and PRA during fetoplacental blood volume depletion. The data indicate that the fetal volume receptors for control of arginine vasopressin secretion are fully functional in the last trimester of gestation and suggests that fetal pAVP and PRA are released as an exponential function of the percent of fetoplacental blood volume depletion. Finally, an isosmotic water shift from the fetal interstitial space to the fetal vascular space is described during fetal hemorrhage.SpeculationIt is suggested that a change in the equilibrium between the forces regulating fluid movement through the fetal capillary membranes, in accordance with Starling's principle, activates isosmotic water fluxes from the fetal interstitial space to the fetal vascular compartment counteracting the effects of fetal blood volume depletion. Therefore, the role of arginine vasopressin (AVP) release during fetal hemorrhage, if any, will be to act as a pressor substance helping to maintain fetal blood pressure. No major effect of AVP on placental membranes was demonstratedin vivo.

ISSN:0031-3998    

出版商:OVID    

年代:1979

数据来源: OVID

摘要:

SummaryTo study the effect of lung expansion at birth on surfactant secretion, we delivered by hysterotomy 11 litters of rabbit pups at 30 days of gestation and divided them into three groups that were killed: 1) after 30 min air-breathing, 2) after 30 min nitrogen-breathing, and 3) after 30 min tracheal occlusion. Each group was compared to a littermate group killed at birth. Groups 2) and 3) continued respiratory efforts for 30 min despite progressive asphyxia. Six additional litters were pretreated with atropine; at delivery one-half of each litter was killed, the remaining pups were subjected to 30 min of hypoxic gas breathing. After sacrifice, alveolar surfactant was recovered by saline lavage and estimated quantitatively on a surface-tension balance. Surfactant concentration at birth was 1.40 ± 0.22 mg/g dry lung and increased to 1.86 ± 0.19 (± SEM) after 30 min air-breathing (P< 0.01). Also, surfactant was increased in the nitrogen-breathing pups (from 1.61 ± 0.35 in littermate controls to 2.41 ± 0.58;P< 0.03), but not to a significant degree in the occluded group (1.34 ± 0.33vs.1.41 ± 0.28), or the atropine pretreated breathing pups (1.77 ± 0.29vs.1.89 ± 0.25).SpeculationThe data indicate that lung expansion at birth enhances surfactant release from intracellular sites and suggest that the vagus nerve mediates this effect. It is possible that the effect of maternal atropine may have clinical significance in preterm infants.

ISSN:0031-3998    

出版商:OVID    

年代:1979

数据来源: OVID

ISSN:0031-3998    

出版商:OVID    

年代:1979

数据来源: OVID

摘要:

SummaryAdministration of thyrotropin-releasing hormone (TRH) to pregnant rabbits at 25 and 26 days of gestation results in increased pulmonary surfactant production by the fetus at 27 days (full term is 31 days). There was 60% more total phospholipid and 150% more phosphatidylcholine (the major component of surfactant) in the lung lavage from the fetuses in the treated group than in that from the controls. Lung lavage from the fetuses in the treated litters contained 13.4 ± 1.6 μg of total phospholipid phosphorus/g lung dry wt and 5.6 ± 1.1 μg of phosphatidylcholine phosphorus while that from the fetuses in the control litters contained only 8.2 ± 1.1 μg and 2.2 ± 0.4 μg, respectively. The phosphatidylcholine/sphingomyelin ratio increased from 1.0 in the lavage from the controls to 2.2 in that from the treated group. These changes in lung lavage phospholipid content and composition are in the direction of increased lung maturation. TRH administration had no effect on the incorporation of choline into phosphatidylcholine in fetal lung slices. These data suggest that TRH stimulates surfactant release rather than synthesis.SpeculationTRH has a physiologic role in fetal lung maturation and surfactant production. It may potentially be used in the prevention of the respiratory distress syndrome in humans.

ISSN:0031-3998    

出版商:OVID    

年代:1979

数据来源: OVID

摘要:

SummaryThe rate of histone phosphorylation in adipose tissue abstracts obtained from adults and newborns by cyclic adenosine mono-phosphate (cAMP)-dependent protein kinase was studied. Aden-sine triphosphate (ATP) had an apparent Km of 0.18 μM. Further kinetic studies indicated that human white adipose tissue is similar to brown adipose tissue of newborn rats in that it probably contains more than one type of soluble cyclic AMP-dependent protein kinase activity.Cyclic AMP activated the human enzyme with maximum velocity reached at 1μM concentration. Cyclic guanosine monophosphate, however, produced only a low level activation of the enzyme, perhaps more dose-dependent when arginine-rich histone served as the phosphate acceptor.The activity in samples of subcutaneous adipose tissue of two age groups of healthy newborns was compared with samples obtained from adult volunteers. Both the basal activity and the cAMP-activated enzymes showed an increase with age. The velocity values for the rate of phosphorylation observed in the presence of relatively high NaCl concentrations were depressed by approximately 50%; the “activity ratio” under these conditions, however, reflected the truein vivostate of activation of the type II protein kinase.It has been confirmed by a series of methodologic experiments that the cyclic AMP dependent protein kinase of adult human white fat exhibits the same properties as the type II enzyme described in rat white adipose tissue. The activity ratio was determined on samples of subcutaneous adipose tissue of different age groups of healthy human newborns and of adult volunteers. The system is highly activated immediately after birth (less than 12 hr) and a subsequent decrease (12–48 hr) in the level of activation is observed.SpeculationThe protein kinase system, its composition, characteristics, and in particular, its level of activation under physiologic and pathologic conditions is of utmost importance in our understanding of the molecular mechanisms of hormonal regulation occurring in infant adipose tissue. Experimental conditions described here allow determinations of the in vivo level of activation of the cyclic AMP-dependent system and after further modification may help to link specific hormonal stimulation with phosphorylation, and, thus, functional changes, occurring in specific intracellular proteins.

ISSN:0031-3998    

出版商:OVID    

年代:1979

数据来源: OVID