摘要:

Lipid emulsions used in parenteral nutrition are prone to peroxidation that may be an important feature of oxygen-associated tissue damage. Incubation of lipid emulsion [Intralipid (IL)] with H2O2and FeCl2increased lipid peroxidation, measurable as increased production of pentane, from 0.39 ≤ 0.33 to 0.99 ≤ 0.18 μM (p < 0.0001). Malondialdehyde was increased from 0.010 ≤ 0.005 mM to 0.380 ≤ 0.025 mM (p < 0.001). Superoxide dismutase and catalase (each 100 U/mL) or vitamin C (10 mM) inhibited pentane and malondialdehyde production (p < 0.0001). Incubation of human erythrocytes in the presence of FeCl2caused 11.0 ≤ 3.2% hemolysis (control 0.95 ≤ 0.14%). Addition of 0.44% IL increased hemolysis to 66.5 ≤ 3.4%, whereas further addition of vitamin E or C significantly inhibited hemolysis to 16.4 ≤ 8.1 and 38.9 ≤ 7.1%, respectively (p < 0.0001). IL was administered i.v. to eight preterm infants. It increased 3− to 28-fold (p < 0.001) the amount of pentane in expired breath. Partly, this increase was due to pentane dissolved in IL as a result of lipid peroxidation during storage. After discontinuing IL infusion, the elimination of pentane was nonexponential, consisting of a rapid and a slow component. According to our results, IL undergoes peroxidation causing free-radical-dependent damage to human cells. We propose that the adverse effects of parenteral IL are partially caused by free oxygen radicals generated by lipid peroxidation.

ISSN:0031-3998    

出版商:OVID    

年代:1991

数据来源: OVID

摘要:

Newly identified forms of electron transfer flavoprotein (ETF) deficiency in two patients with glutaric aciduria type II (GA II) were described. GA II has been attributed to a defect of either ETF or ETF dehydrogenase, resulting in multiple acyl-CoA dehydrogenation deficiency. ETF is a mitochondrial flavoprotein consisting of an α-subunit, β-ETF, a α α-subunit, β-ETF. We used pulse-chase experiments to examine the biosynthesis of ETF in fibroblasts from two patients with GA II. Patient I was a boy with the neonatal onset form, but without congenital anomalies, who is living at age 2 y. A defect of β-ETF biosynthesis was noted in this patient. Patient 2 was a boy with the neonatal onset form with congenital anomalies who died on the 3rd postnatal day. He presented with a peculiar face and polycystic kidneys. In patient 2, both α-and β-ETF were synthesized, but both the subunits were rapidly degraded. The lability of ETF was considered to be the cause of GA II in this patient. These two cases appear to be new forms of ETF deficiency in GA II.

ISSN:0031-3998    

出版商:OVID    

年代:1991

数据来源: OVID

摘要:

Infantile Zellweger syndrome belongs to the group of peroxisomal disorders that lack peroxisomes. Both trihydroxycoprostanic acid (THCA), the precursor to cholic acid, and dihydroxycoprostanic acid (DHCA), the precursor to chenodeoxycholic acid, accumulate in this disease. In previous studies, we have shown that liver peroxisomes are required for the conversion of THCA into cholic acid bothin vitroandin vivoby measuring a defective conversion in infants with Zellweger syndrome. In our present study, the conversion of DHCA into chen-odeoxycholic acid has been measured in an infant with Zellweger syndrome to evaluate the importance of liver peroxisomes for the formation of chenodeoxycholic acid. Coprostanic acidemia was present from the second day of life with high levels of THCA and only trace amounts of DHCA. The conversion of i.v. administered I3H]DHCA into Chenodeoxycholic acid was only 7% compared with the 80% conversion in an analogous study in an adult. There was, however, a rapid incorporation of3H into biliary THCA and, after a lag phase, the 3H was incorporated into biliary cholic acid. After 72 h, 15% of I3H]DHCA was converted to cholic acid. The pool size of DHCA was 1.2 mg/m2and the pool size of both cholic acid and chenodeoxycholic acid was markedly reduced. The renal excretion of cholic acid was more efficient than that of the less polar chenodeoxycholic acid. More polar metabolites of DHCA and THCA are formed in alternative metabolic pathways facilitating renal excretion of these toxic intermediates. We conclude that liver peroxisomes are essential for a normal conversion of DHCA into chenodeoxycholic acid.

ISSN:0031-3998    

出版商:OVID    

年代:1991

数据来源: OVID

摘要:

We measured body composition, resting metabolic rate (RMR), and total energy expenditure (TEE) in a group of adolescents with cerebral palsy (CP) and myelodysplasia (M) aged 13− to 20-y-old using indirect calorimetry and the doubly labeled water method. Fat-free mass (FFM), RMR, and TEE were significantly lower in both the CP and M groups than comparable measurements in a control group of normal adolescent males and females. The ratio of TEE to RMR did not differ between controls and ambulatory M and CP subjects. However, TEE/RMR was significantly lower in the nonambulatory M and CP subjects than in controls (p < 0.01). Our data indicate that energy requirements are reduced in both populations because both FFM and activity are decreased. Although energy requirements were decreased in both groups, the relationships between FFM and body weight differed. FFM and body weight were significantly correlated with RMR only in the M group. These data suggest that the type of paralysis in a handicapped population may affect resting energy expenditure.

ISSN:0031-3998    

出版商:OVID    

年代:1991

数据来源: OVID

摘要:

The development of the transdermal electrical potential (TDP) with postnatal age was studied in neonates born at gestational ages of 25 to 42 wk. The TDP of neonates born at less than 28 wk gestational age was of similar magnitude over the whole skin surface when measured in the first 5 d of life (mean value −5.4 mV; skin surface negative with respect to s.c. tissues). The TDP increased progressively with increasing gestational and postnatal age. The rate of increase of the TDP with post-menstrual age was not accelerated in neonates born prematurely. TDP values of infants born at term were lower than those of adults, but the sites of high and low TDP were similar in both term infants and adults.

ISSN:0031-3998    

出版商:OVID    

年代:1991

数据来源: OVID

摘要:

Short pulses in airway pressure were used to assess the pulmonary mechanical function of nine infants suffering acute respiratory distress syndrome or broncho-pulmonary dysplasia. All patients were intubated, spontaneously breathing, and mechanically ventilated at the time they were examined. The endotracheal tube was disconnected from the ventilator and connected to a mechanical oscillator that produced brief pulses in airway pressure at a rate of two pulses/s. These pulses were applied to the infants airway for 20–30 s, at which time the infant was replaced on the ventilator. The mean airway pressure during the procedure was maintained at the level of the positive and expiratory pressure that was set on the ventilator. Two classes of patients were identified from the pulse response primarily by the presence or absence of a local resonance in the impedance spectra. Similar results were obtained in five other patients who were examined with zero mean airway pressure, suggesting that the pulse response is little influenced by changes in mean lung volume or total lung compliance. Patient classification appeared related to the duration of ventilation therapy and the transition from one class to another was consistent with the development of high peripheral airway resistance and significant volume shunting in the central airways. These results suggest that brief pulses in airway pressure can be used to detect changes in the pulmonary mechanical function of preterm infants that result from long-term ventilation therapy.

ISSN:0031-3998    

出版商:OVID    

年代:1991

数据来源: OVID

摘要:

Air trapping and alveolar hyperinflation may occur during mechanical ventilation in the presence of severe airway obstruction, during fast ventilator rates, and when expiratory time is compromised. Inadvertent positive end-expiratory pressure may occur with air trapping and increased mean airway pressure. The pulmonary artery pressure response to air trapping, produced during volume-regulated time-cycled ventilation, was studied in neonatal lamb lungs, isolatedin situ, and perfused at a constant flow rate (50–75 ml.kg-1min-1), both before and after Ca2+-channel blockade with verapamil (5 mg). The hub of the endotracheal tube was narrowed to a 1.5-mm orifice to produce fixed proximal airway obstruction. Air trapping was then produced by lengthening inspiratory time from 25 to 80%, at zero end-expiratory pressure. The magnitude of inadvertent positive end-expiratory pressure due to air trapping was estimated by end-expiratory occlusion pressure. End-expiratory occlusion pressure was 0.20 ≤ 0.03 kPa (1.7 ≤ 0.2 mm Hg) and 1.60 ≤ 0.01 kPa (11.8 ≤ 1.0 mm Hg), at 25 and 80% inspiratory times, respectively. On lengthening inspiratory time, mean pulmonary artery pressure (mPpa) increased briskly within 30 s followed by a gradual increase over the next 4 min. Verapamil blunted both the brisk and the gradual increase in mPpa on lengthening inspiratory time. Lengthening inspiratory time increased the mPpa by 2.0 ≤ 0.1 kPa (14.7 ≤ 0.8 mm Hg) from baseline, and verapamil reduced this increase to 1.3 ≤ 0.1 kPa (10.1 ≤ 0.6 mm Hg; p < 0.05 by analysis of variance). Verapamil did not affect changes in mean airway and peak inspiratory airway pressures and the magnitude of inadvertent positive end-expiratory pressure caused by lengthening inspiratory time. In the neonatal lamb, the Ca2+-channel-dependent portion of the mPpa response to air trapping amplifies the Ca2+-channel-independent portion, which represents the compressive effects of airway pressure on the pulmonary circulation.

ISSN:0031-3998    

出版商:OVID    

年代:1991

数据来源: OVID

摘要:

The lungs play an important role in the metabolism of vasoactive substances including endogenous amines. The role of pulmonary clearance of circulating norepinephrine has not been well defined in the young lamb (7–8 d of age). Using radiolabeled tracer norepinephrine in acutely instrumented lambs, we determined thein vivopulmonary clearance and spillover rate of norepinephrine under baseline and hypoxic conditions. The fractional extraction of norepinephrine, the percent removed on a single pass through the pulmonary circulation, was 23 ≤ 2%. The corresponding pulmonary clearance rate was 61 ≤ 10 mL/kg/min and the net pulmonary norepinephrine removal rate was 0.41 ≤ 0.14 nmol/kg/min. This clearance represented over 70% of whole body norepinephrine clearance. The spillover of synaptic norepinephrine was 0.22 ≤ 0.13 nmol/kg/rain. During hypoxia, animals showed significant increases in pulmonary artery pressure and resistance. Fractional extraction of norepinephrine decreased to 16 ≤ 3%, p < 0.005. Pulmonary clearance decreased to 31 ≤ 7 mL/kg/min, and net pulmonary norepinephrine removal rate decreased to 0.27 ≤ 0.07 nmol/kg/min. These results demonstrate that pulmonary clearance plays a significant role in norepinephrine clearance in 1-wk-old lambs. Alteration of norepinephrine clearance during physiologic states such as hypoxia may be important in the pathophysiology of altered pulmonary vascular resistance in newborn animals.

ISSN:0031-3998    

出版商:OVID    

年代:1991

数据来源: OVID

摘要:

At birth, there is a marked increase in circulating plasma catecholamine concentrations. This increase is critical to many of the physiologic adjustments to postnatal life. Because the levels observed are higher than those seen in most other physiologic conditions in adults, previous investigators have suggested that the newborn is less sensitive to adrenergic stimulation or that desensitization to adrenergic stimulation occurs rapidly. To investigate this question, we designed experiments to measure myocardial β-adrenergic receptor density and sensitivity before and after exposure to the catecholamine surge at birth in term newborn sheep. We also measured the status of sympathetic innervation, reflected by myocardial norepinephrine content. At birth, plasma catecholamines increased 4− to 6-fold with associated increases in heart rate, blood pressure, and cardiac output. Myocardial β-adrenergic receptor at birth (135 fmol/mg protein) did not change significantly by 6 h of life (157 fmol/mg protein). Myocardial adenyl cyclase activity, reflecting receptor sensitivity, and myocardial sympathetic innervation also did not change. These results suggest that, despite exposure to sustained adrenergic stimulation, myocardial adrenergic effector mechanisms do not change in the newborn sheep at birth.

ISSN:0031-3998    

出版商:OVID    

年代:1991

数据来源: OVID

摘要:

d-Sotalol may be a clinically useful class III antiarrhythmic agent for controlling ventricular arrhythmias in children. Because age-related differences in repolarization currents may contribute to developmental differences in response to antiarrhythmic agents that primarily affect repolarization, the electrophysiologic effects of d-sotalol were compared in Purkinje fibers from neonatal and adult dogs. Significant age-related changes characterized the antiarrhythmic profile of d-sotalol. d-Sotalol (10-4M) significantly prolonged the action potential duration of adult Purkinje fibers (310 ≤ 8 to 380 ≤ 7 ms, p < 0.01) and neonatal fibers (247 ≤ 5 to 342 ≤ 9 ms, p < 0.01). However, the lengthening of action potential duration was significantly greater in the immature age group. d-Sotalol had no significant effect on maximum diastolic potential, action potential amplitude, or phase zero upstroke velocity in normally polarized fibers. In contrast, different electrophysiologic effects were observed in K+-depolarized Purkinje fibers. Superfusion of adult K+-depolarized fibers with d-sotalol suppressed excitability in five (38%) of 13 fibers and significantly decreased action potential amplitude (88 ≤ 2 to 83 ≤ 1 mV, p < 0.05) and phase zero upstroke velocity (180 ≤ 14 to 105 ≤ 3 V/s, p < 0.01) in the other eight fibers. The membrane depressant effects observed in the younger age group were significantly less (no suppression of excitability and a smaller decrease in phase zero upstroke velocity (121 ≤ 22 to 101 ≤ 23 V/s, p < 0.05). The magnitude of action potential duration prolongation by d-sotalol in K+-depolarized fibers was less than in normally polarized fibers. These results suggest that at the clinical level the mechanism of d-sotalol's antiarrhythmic action will depend not only on the developmental maturity, but also on the resting membrane potential of the tissue treated.

ISSN:0031-3998    

出版商:OVID    

年代:1991

数据来源: OVID