摘要:

Benzoate and phenylacetate improve prognosis in inherited urea cycle enzyme deficiencies by increasing waste nitrogen excretion as amino acid acylation products. We studied metabolic changes caused by these substances and their pharmacokinetics in a biochemically different urea cycle disorder, lysinuric protein intolerance (LPI), under strictly standardized induction of hyperammonemia. Five patients with LPI received an intravenous infusion of 6.6 mmol/kg L-alanine alone and separately with 2.0 mmol/kg of benzoate or phenylacetate in 90 min. Blood for ammonia, serum urea and creatinine, plasma benzoate, hippurate, phenylacetate, phenylacetylglutamine, and amino acids was obtained at 0, 120, 180, and 270 min. Urine was collected in four consecutive 6-h periods. Alanine caused hyperammonemia: maximum increase 107, 28-411 µM (geometric mean, 95% confidence interval); ammonia increments were nearly identical after alanine + benzoate (60, 17-213 µM) and alanine + phenylacetate (79, 13-467 µM) (NS). Mean plasma benzoate was 6.0 mM when extrapolated to the end of alanine + benzoate infusions; phenylacetate was 4.9 mM at the end of alanine + phenylacetate. Transient toxicity (dizziness, nausea, vomiting) occurred in four patients at the end of combined infusions, and we suggest upper therapeutic plasma concentrations of 4.5 mM for benzoate and 3.5 mM for phenylacetate. Benzoate and phenylacetate then decreased following first-order kinetics with t1/2s of 273 and 254 min, respectively. Maximal plasma hippurate (0.24, 0.14-0.40 mM) was lower than maximal phenylacetylglutamine (0.48, 0.22-1.06 mM,p=0.008). Orotic acid excretion was 5.62, 1.84-17.14 µmol/kg per h after alanine, but only 1.07, 0.04-25.62 µmol/kg per h after alanine + benzoate (p<0.151) and 2.74,0.01-16.25 µmol/ kg per h after alanine + phenylacetate (p<0.016). Urea excretions were in the same range after all loads. Urinary hippurate nitrogen after alanine + benzoate and phenylacetylglutamine, nitrogen after alanine + phenylacetate accounted for an average of 12 and 22 of that in urea in the first 6 h. Of the benzoate and phenylacetate given, 65 and 51% were excreted in 24 h as hippurate and phenylacetyl-glutamine, respectively; less than 3.5% appeared unchanged in urine.

ISSN:0031-3998    

出版商:OVID    

年代:1986

数据来源: OVID

摘要:

Serum insulin, growth hormone (GH), insulin- like growth factors (IGFs) I and II, cortisol, and albumin concentrations were measured in 15 children with kwashiorkor, 15 with marasmic-kwashiorkor, and 21 with marasmus, before and in the survivors, after nutritional rehabilitation, as well as in 10 underweight and eight normal Egyptian children. We also evaluated arginine-induced insulin and GH secretion. IGF-I concentrations were reduced in the three severely malnourished groups (0.07 ± 0.03, 0.05 ± 0.03, and 0.09 ± 0.09 U/ml, respectively) but returned to normal after refeeding. IGF-II concentrations were low in the kwashiorkor (175 ± 79 ng/ml), marasmic-kwashiorkor (111 ± 57 ng/ml), and marasmic children (128 ± 70.9 ng/ml) and returned to normal after nutritional rehabilitation. Basal GH levels were high in the three severely malnourished groups (21.9, 28.8, and 16.6 ng/ml, respectively) and returned to normal after refeeding (8.1, 6.5, and 6.0 ng/ml, respectively). GH responses to arginine were depressed in the three malnourished groups and improved significantly in marasmic-kwashiorkor and marasmic children after nutritional rehabilitation. Insulin responses to arginine were impaired in kwashiorkor, and marasmic-kwashiorkor children and improved significantly after refeeding. IGF-I levels correlated significantly with percent of expected weight (r=0.52,p<0.001), percent of expected height (r=0.42,p<0.001), and weight/ (height)2index (r=0.34,p<0.01). IGF-I levels correlated positively with insulin levels (r=0.421,p<0.001) and negatively with cortisol concentrations (r=—0.400,p<0.001). It is suggested that effective lipolysis mediated by high GH and possibly low IGF levels, is an important adaptive mechanism to assure fuel (fatty acids) supply for metabolism of brain and peripheral tissues during nutritional deprivation.

ISSN:0031-3998    

出版商:OVID    

年代:1986

数据来源: OVID

摘要:

Although tolazoline is the most commonly used drug in the treatment of neonatal pulmonary hypertension, its mode of action and efficacy remain incompletely understood. In order to study the effects of tolazoline on a high resistance pulmonary circulation and to better understand mechanisms that control pulmonary vascular tone and reactivity in the fetus, we infused tolazoline either continuously or as bolus into the left pulmonary artery of 15 chronically instrumented, normoxic fetal lambs during late gestation. The vasodilatory effects of bolus injections of tolazoline (2.5 mg) were inhibited by the prior administration of the histaminergic receptor blockers, cimetidine (56%), diphenhydramine (56%), or both (100%). During the continuous infusion of tolazoline (4.5 mg/h for 9 min), pulmonary blood flow to the left lung increased from 61 ± 6 ml/min (mean ± SE; control) to 100 ± 10 (peak) at 30 min (P<0.001). However, following this initial vasodilatation, pulmonary blood flow steadily decreased toward control values by 90 min, despite the continued infusion of tolazoline (P<0.001). Although the calcium channel blocker, verapamil, and the a-adrenergic blocker, phentolamine, had little effect on fetal pulmonary blood flow when infused alone, both drugs increased the vasodilatory response to tolazoline (P<0.001). We conclude that tolazoline effects pulmonary vasodilatation by a histaminergic mechanism and that subsequent refractoriness to the drug is a calcium-dependent process which may be partially mediated by an a-adrenergic mechanism.

ISSN:0031-3998    

出版商:OVID    

年代:1986

数据来源: OVID

摘要:

Using intravital microscopy we studied the responses of the jejunal and ileal mesenteric microcirculation to hypertonic meals in neonatal piglets. Test meals were infused through a cannulated segment of proximal jejunum. The intestinal segments were observed under conditions of controlled temperature and humidity, and the velocity of red blood cells through mesenteric arterioles was measured and blood flow calculated. Jejunal flow was not altered from baseline by saline or hypertonic manitol infusion, while significant increases in flow were observed during hypertonic glucose infusion (3.8 × 10-6versus 10.7 × 10-6ml/s,p<0.01). Jejunal glucose infusion did not cause shunting from the ileal microcirculatory bed. We conclude that the infusion of hypertonic glucose causes an increase in jejunal blood flow, but does not result in a change in ileal flow. The increase in flow is a local phenomenon related to glucose absorption in neonatal piglets.

ISSN:0031-3998    

出版商:OVID    

年代:1986

数据来源: OVID

摘要:

Surfactants were labeled in vivo with [3H] choline and the large aggregates of the surfactant were recovered by alveolar wash and centrifugation. The labeled natural surfactants from rabbit, sheep, cat, and pig were injected into the airways of 3-day-old rabbits, and the percent recoveries of the labeled surfactant-associated phosphatidylcholine were measured in alveolar washes, lung tissue after alveolar wash, and in the lungs (alveolar wash plus lung tissue). The rabbit surfactant-associated phosphatidylcholine was cleared from the lungs at a constant 15.6 ± 1.8% per 24 h (mean ± SE) of the injected doses of surfactant that contained from 0.41 to 10.2 µmol phosphatidylcholine. At all times following injection, approximately 50% of the labeled phosphatidylcholine remaining within the lungs was recovered in the alveolar wash and 50% with the lung tissue. The percent clearances for sheep, cat, and pig surfactant phosphatidylcholine in rabbits were 12.5, 16.6, and 16.3% per 24 h, respectively, values not different from that measured for rabbit surfactant. The results documented a slow clearance of exogenously administered surfactant phosphatidylcholine as a fixed percent of the injected dose that was unchanged by species source of the surfactant.

ISSN:0031-3998    

出版商:OVID    

年代:1986

数据来源: OVID

摘要:

A model of nonischemic hypoxia of the jejunum was designed in dogs, by shunting of blood from the inferior vena cava directly into the regional mesenteric arterial supply, thereby lowering the PaO2of the blood that reached the jejunal wall from 98.6 ± 3 to 62 ± 5 mm Hg. Absorption rates of sodium, glucose, fructose, glycine, and the dibasic aminoacid lysine were studied byin situluminal perfusion of a 30-cm proximal jejunal segment with a bicarbonate buffer solution containing phenol red as a nonabsorbable marker for determination of water fluxes. During periods of control, hypoxia, and after discontinuation of the venoarterial admixture (recovery), effluent perfusate was collected and mucosal biopsies were obtained for assay of lactase, maltase and sucrase activity, mucosal ATPase activity and ATP content, and for light- and electron microscopic examination. Mesenteric supply with hypoxic blood was associated with a significant inhibition of Na+,K+-ATPase activity (p<0.001) and a rise in mucosal ATP content (p<0.05). There was a significant reduction in the absorption rates of sodium (p<0.001), glucose, and glycine (p<0.01), but no change in the transport of fructose and of lysine. Brush border enzymes were unaltered. The histological appearance of the mucosa remained normal throughout the experiment, but on electron microscopy a distinct swelling of the enterocyte mitochondria was noted during the hypoxia period. Discontinuation of the venoarterial shunt and return to well-oxygenated mesenteric blood supply to the small gut was associated with a recuperation of Na+,K+-ATPase activity, decrease of mucosal ATP content, improvement of mucosal absorption capacity, and disappearance of the mitochondrial swelling. It is concluded that nonischemic hypoxia of the jejunum can impair Na+,-K+-ATPase-related jejunal absorption functions in the absence of apparent structural damage.

ISSN:0031-3998    

出版商:OVID    

年代:1986

数据来源: OVID

摘要:

The distributions of lymphocyte subsets and monocytes in the peripheral blood mononuclear leukocytes of 72 normal children from 2 months to 135/12yr were examined using quantitative immunofluorescence analysis with monoclonal antibodies. Distinct decreases with age were found in the total leukocyte counts, the percentages and the absolute numbers of peripheral blood mononuclear leukocytes. The percentages of Leu-2a+cells, Leu-7+cells, and Leu-M3+cells significantly increased with age, whereas the percentages of Leu-3a+cells, Leu-4+cells, and 2H7+cells significantly decreased with age. As a result, ratios of Leu-3a+/Leu-2a+decreased with age. No prominent differences with age were found in the proportions of Leu-10+cells and HLA-DR+cells.

ISSN:0031-3998    

出版商:OVID    

年代:1986

数据来源: OVID

ISSN:0031-3998    

出版商:OVID    

年代:1986

数据来源: OVID

摘要:

The maturity ofβ-adrenoceptors in newborn infants was studied in relation to the catecholamine surge during labor. Umbilical blood was collected at birth from 12 infants delivered vaginally and 13 infants delivered by elective cesarean section. Granulocytes and lymphocytes were isolated. Receptor numbers and binding affinity were determined in the granulocytes by incubation with125Iiodohydroxybenzylpindolol. Receptor responsiveness was tested by assessing isoproterenol-induced cyclic AMP accumulation in lymphocytes. Significantly higher plasma noradrenaline, adrenaline, and dopamine concentrations were found in infants born vaginally (108; 8.9; 0.9 nmol/ liter, respectively, median values) as compared with those delivered by cesarean section (11.0; 2.4; 0.2 nmol/liter). No significant differences inβ-adrenoceptor binding sites (receptor number: 39.2 ± 2.6 versus 44.7 ± 5.9 fmol/mg protein and binding affinity: 66.6 ± 7.8 versus 65.0 ± 6.2 pM) or responsiveness (maximal isoprenaline induced cAMP formation 52.4 ± 10.3 versus 40.6 ± 8.9 pmol/106cells) were found between the two groups of infants. Lymphocyteβ-adrenoceptor sensitivity was similar to that found in adults.Theβ-adrenoceptors on whole blood cells seem to be mature at birth and have the same responsiveness as in adults. The higher catecholamine surge during vaginal delivery as compared to elective cesarean section does not seem to affectβ-adrenoceptor function. Our results do not support the idea that reducedβ-adrenoceptor function is the cause of the previously observed inappropriately small cardiovascular and metabolic responses to the exceptionally high plasma catecholamine concentrations at birth.

ISSN:0031-3998    

出版商:OVID    

年代:1986

数据来源: OVID

摘要:

The guinea pig is a small animal species in which the conceptus constitutes a large proportion of maternal weight at term, thereby imposing a major metabolic demand on the mother during pregnancy. In addition the neonatal fat concentration is similar to the human making the guinea pig an interesting model for comparative physiologic study. The purpose of our study was to describe the fetal and maternal physical/chemical growth characteristics of the Hartley albino guinea pig throughout the latter half of gestation. Forty-eight pregnant adult and 122 fetal guinea pigs were sacrificed at intervals throughout gestation and the carcasses analyzed for a variety of growth parameters. The fetal growth rate during the last 8 days of gestation (5.8 g/day) was 9.7 times faster than from 30 to 40 days of gestation (0.6 g/day). The fetal mass comprised 55.4% of the maternal weight gain at term. Fetal energy increased from 403 cal/g at 30 days to 1950 cal/g at term and was paralleled by an increase in fetal fat concentration from 0.3 to 9.8% (wet weight). Nitrogen concentration increased from 0.9% wet weight at 30 days to 2.6% at term. An increasing carbon concentration and carbomnitrogen ratio was also evident. Fetal water concentration declined from 91.6 to 67.8% during latter gestation. On a wet weight basis, the concentration of fetal sodium remained stable throughout the latter half of pregnancy; potassium, magnesium, iron, calcium, and phosphorus concentrations increased. In contrast to the changes in fetal composition, maternal energy, fat, protein, water, sodium, potassium, calcium, phosphorus, magnesium, and iron concentrations remained relatively constant throughout pregnancy. Therefore, close parallels exist between the guinea pig fetus and human fetus with respect to rates of weight gain as well as energy, fat, protein, water, sodium, calcium, and phosphorus composition. Although dissimilar from the human fetus in respect to potassium, magnesium, iron and “chemical maturity,” the fetal guinea pig may be a good model for the study of fetal and perinatal fat matabolism.

ISSN:0031-3998    

出版商:OVID    

年代:1986

数据来源: OVID