摘要:

The present investigation was undertaken to find the differences, if any, in the pattern of nephrotoxic acute renal failure (HgCl2,4.7 mg/kg body weight SC), in the developing rat and its relationship to the renin angiotensin system. No differences in renal cortical renin content were found between 2, 4, and 8 week olds, but plasma renin concentration was highest at 2 weeks and declined with age. Plasma renin was significantly increased in all groups 6 hr after HgCl2injection, and the percentage of increase was highest in the 4 week olds. Despite these differences in initial plasma renin and in changes in plasma renin after HgCl2, the pattern of acute renal failure (as assessed by changes in blood urea nitrogen) was similar in the three groups for the first three days. Subsequently, the 4 and 8 week olds exhibited recovery (blood urea nitrogen began to decline), wheras blood urea nitrogen continued to increase to the fifth day in the 2 week olds. The mortality was highest in this group. No simple correlation was observed between basal renal renin, plasma renin, the increase in plasma renin following HgCl2injection, and the pattern or severity of acute renal failure.SpeculationThe delayed recovery of renal function in younger rats may be due to a limitation in their ability to eliminate nephrotoxin imposed by immaturity of both glomerular and tubular function.

ISSN:0031-3998    

出版商:OVID    

年代:1980

数据来源: OVID

摘要:

Increased concentrations of carcinoembryonic antigen (CEA) have been reported in the sera and sputum of patients with cystic fibrosis. We have found significantly higher concentrations of CEA in both extracted and unextracted saliva of patients with cystic fibrosis compared to age-matched controls and a comparable group of patients with bronchial asthma. The mean CEA concentrations in saliva were also somewhat higher in patients with more severe respiratory disease. The concentration of CEA in the saliva of obligate heterozygotes was similar to healthy controls. This suggests that increased salivary CEA in patients with cystic fibrosis relates to the expression of the disease rather than the genetic predisposition.SpeculationIncreased salivary carcinoembyronic antigen (CEA) in cystic fibrosis may reflect primary changes in the secretion of glycoproteins by exocrine glands. This could result in abnormal properties of these secretions.

ISSN:0031-3998    

出版商:OVID    

年代:1980

数据来源: OVID

摘要:

Prostaglandins play an important role in renal physiology. We have studied the prostaglandin synthetase system in 10 human newborn kidneys ranging from 22 to 40 weeks of gestation who succumbed within 40 hr postnatally. Slices of medulla and cortex were incubated within 2 hr of death in a medium containing 50 μg arachidonic acid and 50 μCi [3H]arachidonic acid. The incorporation of [3H]AA into prostaglandin (PG)E and PGF was determined at 30-min intervals in medulla and cortex tissue and in the incubation media over 120 min and at 180 min, using silicic acid chromatography and scintillation counting. The study showed that biosynthesis of the primary prostaglandins occurs mainly in the renal medulla as early as 22 weeks of gestation, with the biosynthetic activity increasing concomitantly with advanced gestation. The ratio of PGE to PGF in the medulla and cortex was always greater than 1. The highest ratio was obtained in kidneys from neonates born before 28 weeks of gestation. Because prostaglandins are biosynthesized in the neonatal kidney, it is conceivable that hemodynamic and fluid and electrolyte homeostasis functions of prostaglandins may exist at this very early stage of development.SpeculationBecause prostaglandins are biosynthesized early in the development of the neonatal kidney, it is conceivable that hemodynamic and fluid and electrolyte homeostasis functions for prostaglandins might exist at this very early stage of development. Further information into the significance of these findings awaits measurement of age-dependent biologic activity profiles of prostaglandins and their metabolites and prostaglandin-metabolizing enzymes which influence the net production of renal prostaglandins.

ISSN:0031-3998    

出版商:OVID    

年代:1980

数据来源: OVID

摘要:

The age-, race-, and sex-specific distributions for plasma cholesterol (CH) and triglyceride (TG) are described for the 13,655 individuals under 20 years of age who were examined at the first visit (visit I) of the Prevalence Study of the Lipid Research Clinics (LRC) Program. Composite findings are presented from the seven North American LRC's where children were included in the target population. Cholesterol values are higher for blacks than for whites, but triglyceride values are higher for whites than for blacks. In both the CH and TG distributions for the combined races, the mean values for females are generally higher than for males. For cholesterol, consistent age-associated differences occur. On average, the CH values peak in late childhood and decline during adolescence. The decrease in mean values for CH is most marked for white males. The values for TG tend to increase in early adolescence. This report expands the available information about lipid distributions in young populations and describes the extent of the variation in plasma lipids associated with race and sex for each year of age, 0 to 19 years.SpeculationThe pattern of age-associated differences found in these population-based, cross-sectional surveys points to the need for prospective studies of lipid levels in cohorts examined before puberty and followed throughout adolescence and into early childhood. Such longitudinal studies may reveal the biological explanation for the age-curve of the mean values for lipids.

ISSN:0031-3998    

出版商:OVID    

年代:1980

数据来源: OVID

摘要:

To assess the functional maturity of adrenergic modulation of plasma concentration of glucose, as well as immunoreactive glucagon (IRG) and immunoreactive insulin (IRI) secretion in utero, adrenergic agonists with or without β (propranolol) or α (phentolamine) antagonists were infused to the chronically catheterized sheep fetus (n= 35) late in the third trimester. Mean ± S.E. days at study was 129.5 ± 1.5; term is 150 days. In 9 separate studies at gestational age 129 ± 1 days, the infusion of saline for 3 hr was not associated with significant changes in the basal levels of glucose, IRG, or IRI.With epinephrine, 6 μg/min (n= 6) glucose rose from 16.7 ± 3.6 to 41.9 ± 9.7 mg/dl, IRG rose from 75 ± 8 to 219 ± 45 pg/ml, and IRI fell from 22.6 ± 1.7 to 12.7 ± 3.5 microunits/ml (P< 0.05 for each). Propranolol alone (n= 4) did not alter basal glucose or IRG but significantly suppressed IRI. Propranolol did, however, markedly attentuate the rise in glucose and IRG while exaggerating the fall in IRI during epinephrine infusion. Qualitatively similar but smaller responses were obtained with epinephrine, 0.4 μg/min (n= 10). Similarly, elevation of glucose and suppression of IRI was obtained with norepinephrine, 2 μg/min (n= 5), but IRG levels did not rise significantly. α-Adrenergic blockade alone augmented IRI from 18 ± 3 to 38 ± 5 microunits/ml without affecting glucose or IRG concentrations; during a blockade, norepinephrine infusion failed to induce the rise in glucose, IRG remained unchanged, and IRI remained elevated (n= 5). 2-Deoxy-D-glucose, 200 mg IV over 30 min, did not affect glucose, IRG, or IRI (n= 5). Thus, appropriate adrenergic modulation of plasma concentrations of glucose, and of IRG and IRI secretion is established in the third trimester.SpeculationMany of the metabolic adaptations that characterize the transition from intrauterine to extrauterine energy homeostasis are suggestive of a catecholamine effect. These changes include a surge in plasma immunoreactive glucagon concentrations, low immunoreactive insulin levels, an initial fall followed by stabilization of blood glucose, and a rapid rise in free fatty acid levels. An abrupt but brief increase in arterial plasma concentrations of epinephrine and norepinephrine also occurs at birth. In the present studies, infusion of epinephrinein uterosimulated those changes that usually occur after birth, thereby suggesting that catecholamines are a major trigger for neonatal energy adaptations that involve insulin and glucagon secretion.

ISSN:0031-3998    

出版商:OVID    

年代:1980

数据来源: OVID

摘要:

Various metabolic studies were performed in a patient with the idiopathic Fanconi syndrome in whom constant ketonuria suggested that organic acidemia might contribute to the metabolic acidosis. Glucose intolerance with a diminished insulin release was found after PO or IV glucose loads and after glucagon administration. An insulinopenic “diabetes-like” state has not previously been described in such patients. The patient had impaired galactose-glucose interconversion, elevated blood lactate levels, reduced pyruvate levels, and an increased lactate:pyruvate ratio. Hepatomegaly and hypoglycemia were not present, and liver and muscle biopsies revealed no enzymatic evidence of glycogenosis. The erythrocyte UDP galactose transferase activity was normal.The patient failed to convert fructose to glucose and had a rise in blood lactate after ethanol administration. Further studies revealed no production of glucose after alanine or glycerol administration, each test being associated with elevated blood lactate levels and, after alanine, an increased lactate:pyruvate ratio. The lactate:tpyruvate ratio was elevated after glucagon administration with increased lactate and reduced pyruvate concentrations.SpeculationThe increased lactate:pyruvate ratio, abnormal galactose-glucose, and pyruvate-lactate interconversions suggest an altered intracellular redox state with an abnormally high NADH:NAD+ratio.

ISSN:0031-3998    

出版商:OVID    

年代:1980

数据来源: OVID

摘要:

In adults of several species including man, a small transient decrease in serum calcium concentration follows glucagon administration in doses of 1 to 10 mg/kg. The effects of maturation and insulin on this phenomenon were assessed by comparing the response of newborn and adult rats to equivalent doses of glucagon with and without prior insulin administration. After injection of 1 μg/g of glucagon, the decrease in serum calcium concentration at 60 min was significant in the newborn rats (-1.75 mg/dl; P < 0.001) and not significant in the intact adults (-0.07 mg/dl; P > 0.1).In pancreatomized adults, the decrease in serum calcium after the same dose of glucagon became significant (-1.23 mg/dl;P≤ 0.01). This hypocalcemic effect was prevented in the pancreatectomized adult rat if insulin in a dose of 0.01 μg was given 15 min before glucagon. In the newborn rats, the same dose of insulin decreased the hypocalcemic effect, but the change was still significant (-0.74 mg/dl;P≤ 0.01).Glucagon decreased serum calcium at one hr in newborn rats but not in adults. After pancreatectomy, the adult response to glucagon was significant and similar to that of the newborn. Insulin cancelled this effect of glucagon in the pancreatectomized adults and reduced it in the newborns.SpeculationHypocalcemia in the neonatal period is a common and probably multifactorial disorder. Glucagon is known to be a hypocalcemic agent; this effect is decreased by insulin. Because insulin secretion is sluggish in the neonatal period, glucagon may have a clinically significant effect on serum calcium concentration at this time.The frequency and severity of hypocalcemia within the first 48 hr of life are increased by prematurity, perinatal trauma, hypoxia, and maternal diabetes (3,10). Functional hypoparathyroidism has been demonstrated in some of these situations (3,10), but not all instances of hypocalcemia can be explained on this basis (3). Inasmuch as neonatal hypocalcemia is evidently a multifactorial disorder, all agents capable of affecting calcium homeostasis deserve consideration. Glucagon can lower serum calcium concentration in a variety of mammals including man (2, 6–9, 11), but no studies of this phenomenon in the neonatal period have been reported. Grajwerel al.(5) have pointed out that a large increase in immunoreactive plasma glucagon occurs within the first two hr after delivery. Because the newborn infant is particularly susceptible to disturbances of calcium homeostasis, we designed the following experiments to test the effects of maturation on the response of serum calcium concentration to exogenous glucagon.

ISSN:0031-3998    

出版商:OVID    

年代:1980

数据来源: OVID

摘要:

Parathyroid extract (PTE), dibutyrylcyclic AMP (dbcAMP), adenosine cyclic 3':5'-monophosphate (cAMP), calcitonin (CT), and calcium chloride were infused separately into anesthetized, sham-operated, or TPTX vitamin D-fed adult rats to examine the effect of these calciotropic agents on fractional excretion (FE) of α-aminoisobutyric acid (AIB), and phosphate anion (Pi). AIB is a nonmetabolizable amino acid.Inulin clearance, FEAIB, and FEPiwere stable in the intact (n= 10) and TPTX rat (n= 10). TPTX decreased FEaib, and FEPisignificantly (P< 0.001 for both). PTE and dbcAMP both increased FEaib in the intact rat (P< 0.001); failure to obtain this response in the TPTX animal was a key finding. PTE and dbcAMP increased FEPi(P< 0.001) in both the intact and TPTX animal. CT was the only agent (versusPTE, dbcAMP, adenosine cyclic 3‘:5’-monophosphate, and CaCl2) to increase FEAIB(P< 0.001) in the TPTX rat; furthermore, it was the only agent that did not increase FEPiin the TPTX rat although it had hypocalcemic and hypophosphatemic effects. Changes in inulin clearance or plasma concentration of AIB, following infusion of calciotropic agents, do not explain the unique responses in FEAIBin the TPTX rat.Our findings suggest that hyperaminoaciduria induced by parathyroid hormone and cyclic nucleotide in the intact animal may be mediated by CT. Hyperphosphaturia is not a necessary response to small-dose (25 milliunits/kg.hr) infusions of CT.SpeculationIntracellular calcium in renal epithelium may be the final determinant of hyperaminoaciduria in hyperparathyroidism.

ISSN:0031-3998    

出版商:OVID    

年代:1980

数据来源: OVID

摘要:

Prenatal diagnosis was requested by a family at risk for metachromatic leukodystrophy (MLD). An examination of the family leukocyte arylsulfatase A profile revealed that the mother had pseudo arylsulfatase A deficiency. Cultured amniotic fluid cells were deficient in arylsulfatase A, so two possibilities were indicated: the fetus was affected with MLD or had the pseudodeficiency phenotype. The only known biochemical test to differentiate the two enzyme deficient phenotypes is cerebroside sulfate loading of growing fibroblasts. The pseudodeficient cells hydrolyze the incorporated sulfatide as efficiently as control cells, whereas MLD cells show no hydrolysis. Application of this test to the at risk cultured amniotic fluid cells resulted in appreciable uptake of the sulfolipid, but no hydrolysis. Control amniotic fluid cell cultures hydrolyzed 82 to 95% of the incorporated sulfatide. Therefore, an affected fetus was indicated. Fibroblasts derived from the aborted fetus showed a deficiency of arylsulfatase A and a similar inability to hydrolyze cerebroside sulfate in the loading test. The loading technique allowed the prenatal diagnosis of MLD when the arylsulfatase A analysis was equivocal.SpeculationIn metachromatic leukodystrophy families with pseudo arylsulfatase A deficiency, the usual enzyme assays on cultured amniotic fluid cell extracts fail to differentiate between the fetus with the affected phenotype and the fetus with the pseudodeflciency phenotype. The cerebroside sulfate loading test in growing cultured amniotic fluid cells allowed this discrimination. It is important to examine the family enzyme profile for the pseudodeficiency phenotype as a prerequisite hi the prenatal diagnosis of metachromatic leukodystrophy to avoid the erroneous identification of a pseudo-deficient fetus as a metachromatic leukodystrophy fetus.

ISSN:0031-3998    

出版商:OVID    

年代:1980

数据来源: OVID

摘要:

Studies of L-thyroxine T4kinetics and placental transfer were conducted in pregnant rats during the last days of gestation using radioiodine labeled and unlabeled T4. The maternal T4secretion rate was 53.0 ± 6.9 ng/hr/100 g body wt. The placental transfer rate was 0.463 ± 0.196 X 10-3/hr at 18 days and 1.516 ± 0.147 X 10-3/hr at 20 days. From these results, we calculated that at 20 days of gestation, 80 ± 8 pg/hr were transferred to the fetus, less than 1% of the fetal production rate. Inasmuch as we have demonstrated that little placental transfer of T4occurred during these studies, we conclude that the fetal rat hypothalamo-pituitary-thyroid axis develops autonomously.SpeculationThe present data plus the fact that the rats are hypothyroid at birth support the concept of an autonomous development of the hypothalamic-pituitary-thyroid axis. It suggests that the rat can serve as a useful model for development of this axis in the human.

ISSN:0031-3998    

出版商:OVID    

年代:1980

数据来源: OVID