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Biomedical subjects

A Jobe

Publications and source records attributed to A Jobe.

At least 19 recordsLinked to original sources
PubMed2001

The interactive effects of endotoxin with prenatal glucocorticoids on short-term lung function in sheep.

OBJECTIVE: Previously we have shown that neonatal lung function in sheep after preterm birth is profoundly enhanced by intra-amniotic injection of endotoxin, with a magnitude at least equal to that induced by maternal betamethasone administration. This study investigated the effects of betamethasone on lung maturation and growth in the presence of inflammation by treating sheep with both maternal intramuscular betamethasone and intra-amniotic endotoxin injections. STUDY DESIGN: Time-mated pregnant ewes at 118 days' gestation were allocated at random to receive maternal intramuscular or intra-amniotic saline solution injection (n = 10), maternal intramuscular betamethasone injection (0.5 mg/kg; n = 7), intra-amniotic endotoxin injection (20 mg Escherichia coli B055;B5; n = 11) by ultrasonographic guidance, or both betamethasone and endotoxin injections (n = 7). The lambs were delivered abdominally at 125 days' gestation (term is 150 days' gestation), and the neonates were ventilated for 40 minutes before postmortem examination. RESULTS: Combined treatment with betamethasone and endotoxin resulted in significantly greater improvements in neonatal lung function than occurred after treatment with either agent alone, and this effect was not accompanied by a further increase in surfactant levels. The reduction in birth weight that is seen after maternal betamethasone treatment was not seen when this treatment was combined with endotoxin. Endotoxin treatment resulted in inflammatory responses in cord blood and alveolar wash, and these responses were not inhibited by betamethasone treatment. There were no pregnancy losses. CONCLUSION: Both intra-amniotic endotoxin injection and maternal intramuscular betamethasone injection promoted fetal lung maturation. When these treatments were combined, there were additive effects on short-term postnatal lung function but not on surfactant levels. Endotoxin negated the growth restriction in sheep caused by maternal betamethasone treatment. These findings provide evidence that the lung maturation induced by glucocorticoids and that induced by endotoxin are mediated by different mechanisms.

Acute-Phase Reaction↗
PubMed2000

Virtual seminars for disseminating medical nutrition education curriculum ideas.

There is a need and a desire for educators working toward implementation of nutrition in medical schools and residency programs to share ideas and materials. The World Wide Web enables computer-mediated communications through which a medical nutrition curriculum could be discussed; however, existing formats lack focus and structure. In January 1999, a virtual seminar that focused on nutrition education in medical schools and residency programs was conducted. The seminar, titled "Making Room for Nutrition Education, was sponsored by organizations that have active medical nutrition educators. The seminar included 5 topics discussed over a 4-d period. The transcript was made available at http://www.preventivenutrition. com. There were 119 registered participants. Responses to a postseminar questionnaire were positive; there was interest in an ongoing series of virtual seminars.

Curriculum↗
PubMed2000

Surfactant metabolism in SP-D gene-targeted mice.

Mice with surfactant protein (SP)-D deficiency have three to four times more surfactant lipids in air spaces and lung tissue than control mice. We measured multiple aspects of surfactant metabolism and function to identify abnormalities resulting from SP-D deficiency. Relative to saturated phosphatidylcholine (Sat PC), SP-A and SP-C were decreased in the alveolar surfactant and the large-aggregate surfactant fraction. Although large-aggregate surfactant from SP-D gene-targeted [(-/-)] mice converted to small-aggregate surfactant more rapidly, surface tension values were comparable to values for surfactant from SP-D wild-type [(+/+)] mice. (125)I-SP-D was cleared with a half-life of 7 h from SP-D(-/-) mice vs. 13 h in SP-D(+/+) mice. Although initial incorporation and secretion rates for [(3)H]palmitic acid and [(14)C]choline into Sat PC were similar, the labeled Sat PC was lost from the lungs of SP-D(+/+) mice more rapidly than from SP-D(-/-) mice. Clearance rates of intratracheal [(3)H]dipalmitoylphosphatidylcholine were used to estimate net clearances of Sat PC, which were approximately threefold higher for alveolar and total lung Sat PC in SP-D(-/-) mice than in SP-D(+/+) mice. SP-D deficiency results in multiple abnormalities in surfactant forms and metabolism that cannot be attributed to a single mechanism.

1,2-Dipalmitoylphosphatidylcholine↗
PubMed2000

Three children with a syndrome of obesity and overgrowth, atypical psychosis, and seizures: a problem in neuropsychopharmacology.

Three children presented with a complex syndrome of atypical psychotic and extremely immature behavior, obesity and overgrowth, borderline retardation, and seizures (prominent in two). Weight overgrowth exceeded height overgrowth and was stratospheric (up to 8 SD above mean). Obesity seemed related to lack of satiety. The cases fit no known condition: hypothalamic damage, Sotos' syndrome, and Prader-Willi syndrome were excluded. Empirical treatment with anticonvulsants (carbamazepine and acetazolamide) together with psychotropic agents (selective serotonin reuptake inhibitors and risperidone) controlled seizures, improved behavior, and stopped weight gain in each patient. We have not found this syndrome previously described. The etiology is unknown: perinatal encephalopathy could be a factor in the two patients with prominent seizures; in the third, familial major affective disorder is implicated. Medication responses suggest a low-serotonin state underlying the lack of satiety, an imbalance of serotonin and noradrenergic modulation in the hypothalamus, and epileptogenic disorders (or affective disorder responsive to anticonvulsants in one case) involving these same systems.

Anticonvulsants↗
PubMed1996

Surfactant protein B metabolism in newborn rabbits.

Surfactant protein B (SP-B) is critical to the biophysical function of surfactant. To characterize its metabolism in vivo in the newborn, we administered [35S]methionine and [3H]palmitate to newborn rabbits intravascularly. Three groups of 4 rabbits per group were killed at each of 4 time points followed by isolation of SP-B from alveolar wash and lamellar bodies. The labeling kinetics for alveolar wash associated SP-B and saturated phosphatidylcholine (Sat PC) had similar patterns. To characterize SP-B clearance from the airspace, rabbit SP-B was iodinated, mixed with [14C]dipalmitoylphosphatidylcholine and given by intratracheal injection. Alveolar washes and lamellar bodies were recovered from 4 animals at each of 7 time points. Both SP-B and Sat PC were cleared slowly from the total lung (half-life values approximately 25 h). However, SP-B was cleared more rapidly from the airspaces than was Sat PC. The ratio of [125I]SP-B to [14C]Sat PC in lamellar bodies increased 2-fold by 8 h. These results support the concept of linked secretion and clearance pathways for SP-B and Sat PC, although small differences in reuptake were detected.

1,2-Dipalmitoylphosphatidylcholine↗
PubMed1996

Minimum interval from fetal betamethasone treatment to postnatal lung responses in preterm lambs.

OBJECTIVE: We hypothesized that fetal betamethasone exposure for < 24 hours would improve postnatal lung function in preterm lambs. STUDY DESIGN: Singleton fetal sheep were randomized to receive by ultrasonographically guided fetal injections of 0.5 mg/kg betamethasone or saline solution either 8 or 15 hours before preterm delivery and postnatal assessment of lung function. RESULTS: After the 15-hour fetal treatment-to-delivery interval, betamethasone-treated lambs had twofold improvement in compliance and lung volumes, a fourfold to fivefold decrease in edema index, and higher blood pressures than saline solution-treated lambs. Postnatal lung function or lung volumes did not improve for the 8-hour treatment-to-delivery interval, although betamethasone decreased the pulmonary edema and increased the postnatal blood pressure. CONCLUSIONS: The minimal interval from fetal exposure to corticosteroids to delivery for improved postnatal lung function was between 8 and 15 hours. Corticosteroid effects on pulmonary edema and blood pressure occurred within 8 hours.

Animals↗
PubMed1995

Effects of fetal corticosteroid treatments on postnatal surfactant function in preterm lambs.

Effects of prenatal corticosteroid on the properties of surfactant have not previously been evaluated. A single ultrasound-guided fetal injection with 0.5 mg/kg betamethasone 48 h before delivery of preterm lambs at 134- to 135-days gestation improved oxygenation, lowered the ventilatory pressures required to maintain arterial PCO2 between 30 and 40 Torr and decreased the protein leak of albumin from the intravascular to the alveolar space. This dose of glucocorticoid did not alter surfactant-saturated phosphatidylcholine pool sizes in the airspaces of preterm lambs. However, the treatment changed the characteristics of the surfactant recovered from the ventilated preterm lambs. The in vitro conversion from heavy to light subtype surfactant decreased from 59% for the saline-treated lambs to 37% for the corticosteroid-treated lambs after 180 min of surface area cycling (P < 0.02). Surfactant from the corticosteroid-treated lambs also increased the dynamic compliance of preterm surfactant-deficient rabbits more than did surfactant from the saline-treated lambs (P < 0.05). Prenatal treatment of preterm lambs with betamethasone improved the functional characteristics of surfactant without significant effects on the alveolar surfactant pool sizes.

Animals↗
PubMed1994

Ontogeny and effects of exogenous surfactant treatment on SP-A, SP-B, and SP-C mRNA expression in rabbit lungs.

The aims of the present study were to first characterize the ontogeny of mRNAs encoding the principal surfactant proteins SP-A, SP-B, and SP-C in rabbit lung tissues, followed by an evaluation of the effect of exogenous surfactant administration on endogenous expression of mRNA levels. Lung tissues were collected from New Zealand White rabbits on days 19, 21, 24, 26, 28, 30 of gestation, 1 day and 10 days after birth, and as adults. SP-A, SP-B, and SP-C mRNAs were first detected on gestational days 26, 24, and 19, respectively. The specific levels of these mRNAs generally increased to gestational day 28 and decreased transiently on 1 day of life. Adult values remained lower than those noted at 30 days gestation. For the second study, 29-day-gestation preterm rabbits were given either one or two treatment doses of natural surfactant or an organic solvent extract of natural surfactant, and mRNA levels were measured 10 or 24 h later. No effect of surfactant treatments, type of surfactant, or dosage (1 or 2 treatments) was noted on SP-A, SP-B, or SP-C mRNA expression. These data indicate that the mRNA expression for the three major surfactant proteins was highest late in gestation in developing rabbits and that exogenous surfactant treatment was not associated with significant changes in SP-A, SP-B, or SP-C mRNA levels.

Animals↗
PubMed1994

Surfactant subtypes. In vitro conversion, in vivo function, and effects of serum proteins.

Surfactant in the alveolar space can be separated into heavy and light subtypes by differential centrifugation or on isopyknic sucrose density gradients. The conversion from heavy subtypes to light subtypes occurs in vitro by surface-area cycling. However, the function of light subtypes made by cycling and substances that might influence in vitro conversion have not been evaluated. Therefore, we compared the in vivo function of the heavy and light subtypes isolated from rabbit surfactant and similar density fractions prepared in vitro by surface-area cycling. We then asked if serum, globulin, or albumin would alter the in vitro conversion. The function of surfactant fractions was studied in vivo by treating surfactant-deficient 27 d gestational age preterm rabbits with 50 mg/kg of heavy or light subtype surfactant. Dynamic compliance values and lung volumes from PV curve measurements showed that heavy subtypes had superior in vivo function compared with light subtypes independent of in vivo or in vitro sources (p < 0.01). Light subtypes prepared in vitro lost surfactant function and were similar to in vivo light forms. When serum proteins were added to the heavy subtype surfactant, the conversion rate from heavy to light subtypes was accelerated. Serum accelerated conversion more than globulin, and the serine proteinase inhibitor diisopropylfluorophosphate blocked the conversion. Albumin had no significant effect. The increased rate of conversion caused by serum identifies a new mechanism for surfactant inactivation that could occur with lung injuries associated with increased alveolar protein.

Animals↗
PubMed1994

Surfactant protein A labeling kinetics in newborn and adult rabbits.

Surfactant protein A (SP-A), the major hydrophilic protein specifically associated with surfactant, has multiple metabolic and host defense functions as well as primary surfactant biophysical functions in association with the other surfactant proteins and lipids. To characterize its kinetics of secretion and clearance from the airspace, we measured specific activity-time curves for alveolar and lamellar body associated SP-A following the intravascular and/or intratracheal administration of the radiolabeled precursors Tran 35S-label containing primarily methionine and cysteine or [3H]methionine to newborn and adult rabbits. Alveolar SP-A specific activity peaked 30 min after precursor injection in both newborn and adult rabbits, and labeled SP-A was not detected in lamellar bodies until after 2 h. In newborns, a second peak of labeled SP-A appeared at 15 h. In both newborns and adult rabbits, lamellar body specific activity-time curves were most consistent with SP-A entering lamellar bodies via a recycling pathway from the airspaces. The airspace clearance of SP-A in adult rabbits had a biologic half-life of about 4.5 h. There was very little decrease in SP-A specific activity in the newborn rabbits, indicating minimal catabolism. These studies demonstrate secretion of endogenously synthesized SP-A by a pathway separate from lamellar bodies. The kinetics of secretion of SP-A and the surfactant phospholipid in newborn and adult rabbits indicate separate metabolic pathways.

Animals↗
PubMed1993

Single dose versus two doses of betamethasone for lung maturation in preterm rabbits.

Most previous studies of induced lung maturation have used fetal exposures to multiple doses of hormones, and such treatments are associated with fetal growth retardation in rodents and rabbits. This study was designed to evaluate whether single-dose maternal corticosteroid treatments could induce lung maturation without causing fetal growth retardation. Lung maturation was evaluated in 27-d gestational age rabbits by measurements of lung function after preterm delivery and ventilation. Lung function was assessed by measurements of ventilatory requirements, responses to exogenous surfactant, measurements of the recovery of intravascular albumin in the lungs, and surfactant pool sizes. As demonstrated previously, 0.1 mg/kg betamethasone (1 mg = 2.13 mumol betamethasone) given 48 and 24 h before delivery caused both growth retardation (birth weight 20% lower than controls, p < 0.01) and lung maturation (improved compliance, decreased radiolabeled albumin recoveries) despite lower alveolar saturated phosphatidylcholine pool sizes (p < 0.05 versus controls). A single dose of 0.2 mg/kg betamethasone given 48 h before delivery had an equivalent effect on birth weight as the divided doses of 0.1 mg/kg betamethasone, with the only lung maturational effect being a decrease in recovery of labeled albumin in alveolar washes (p < 0.01). A single dose of 0.1 mg/kg betamethasone given 48 h before delivery decreased birth weight by 9.4% (p < 0.01 versus control) but had no effect on any of the lung maturation indicators. Fetal lung maturation caused by maternal corticosteroid is associated with global fetal growth retardation, and a single low dose of corticosteroid can cause growth retardation without inducing lung maturation.(ABSTRACT TRUNCATED AT 250 WORDS)

Albumins↗
PubMed1992

Effects of antenatal thyrotropin-releasing hormone, antenatal corticosteroids, and postnatal ventilation on surfactant mobilization in premature rabbits.

OBJECTIVE: The effects of antenatal hormones on postnatal surfactant mobilization were evaluated in preterm rabbits. STUDY DESIGN: Pregnant rabbits were treated with vehicle, betamethasone, or thyrotropin-releasing hormone for 2 days before cesarean section at 29 days' gestation (term 31 days). Newborns were mechanically ventilated or allowed to spontaneously breathe, and groups were compared by analysis of variance. RESULTS: Neither antenatal corticosteroids nor thyrotropin-releasing hormone increased radiolabeled precursor incorporation, alveolar wash or total lung saturated phosphatidylcholine pools, lung clearance of radiolabeled rabbit surfactant, or estimated net secretion of saturated phosphatidylcholine. However, saturated phosphatidylcholine pools in alveolar wash increased 2.7-fold during the first 24 hours in spontaneously breathing rabbits versus 2.1-fold in mechanically ventilated thyrotropin-releasing hormone-treated and control rabbits (p less than 0.05). In addition, estimated net secretion of precursor-derived saturated phosphatidylcholine was 50% higher after 24 hours in spontaneously breathing rabbits. CONCLUSION: Mechanical ventilation may have hindered the mobilization of surfactant saturated phosphatidylcholine pools to the alveolar space after birth in preterm rabbits, but maternal hormonal therapies did not appear to influence this adaptive process or change surfactant metabolism.

Adrenal Cortex Hormones↗
PubMed1992

Antenatal ambroxol effects on surfactant pool size and postnatal lung function in preterm ventilated rabbits.

Following maternal treatments with 50 mg/kg/day ambroxol for 2 or 3 days before delivery at 28 days gestation, preterm rabbits were ventilated to evaluate lung function. Subsequently, surfactant saturated phosphatidylcholine (SatPC) pool sizes were measured. One half of the ambroxol treated and control rabbits were given surfactant at delivery. Although surfactant improved lung function comparably for control and ambroxol treated rabbits, ambroxol treatments did not change ventilatory pressure requirements, compliances, or the recovery of intravascular labeled albumin in the lungs. Ambroxol treatments tended to increase lung volumes as evaluated by pressure-volume curves. The ambroxol treatments significantly increased lung tissue SatPC by 22%, but there were no changes in alveolar SatPC pool values. These results do not indicate a large effect of ambroxol on lung function in preterm rabbits.

Ambroxol↗
PubMed1991

Leakage of macromolecules in ventilated and unventilated segments of preterm lamb lungs.

The movement of macromolecules into and out of unventilated lung segments was evaluated in prematurely delivered and ventilated lambs. Seven lambs at 130 days gestational age had a bronchial balloon placed at birth before the first breath to obstruct the left lower lobe. Surfactant and 131I-albumin were instilled into the left lower lobe while surfactant and 125I-albumin were instilled into the remaining lung, and 70,000 molecular weight [3H]dextran was given into the vascular space at birth. Twenty-five percent of the lung by weight was not ventilated, and 24% of the total leak of dextran from the vascular space was recovered in the unventilated lungs at 3 h. An epithelial leak of protein from the two lung regions was documented by the loss of 11.4 and 18.4% of the labeled albumins in the nonventilated and ventilated lung regions, the appearance of 4.9 and 7.5% of the airway-instilled albumin in the vascular space from the nonventilated and ventilated lung regions, and the recovery of the labeled albumins in the carcasses of the lambs. The bidirectional flux of macromolecules was larger in the ventilated than in the nonventilated lung regions, indicating that ventilation can increase the leak of protein in the preterm lung. The lung areas that were never exposed to ventilation or oxygen also demonstrated a large bidirectional flux of macromolecules, a finding not present in the fetus, fullterm newborn, or adult. These findings indicate that ventilation is not solely responsible for the increased protein leak found in preterm lungs.(ABSTRACT TRUNCATED AT 250 WORDS)

Albumins↗
PubMed1991

Corticosteroid and thyrotropin-releasing hormone effects on preterm sheep lung function.

Four groups of twin sheep fetuses were catheterized at 121 days of gestational age and intravenously infused with saline, 0.75 mg.kg-1.h-1 cortisol for 60 h, five intermittent bolus injections of 5 micrograms/kg thyrotropin-releasing hormone (TRH) at 12-h intervals, or both hormones before delivery at 128 days. At birth, the lambs were randomized to receive surfactant or no treatment. Surfactant treatment improved lung function of all the groups. Corticosteroids alone and in combination with TRH improved compliance and gas exchange as well as pressure-volume curves. Corticosteroids alone dramatically decreased the recovery of intravenously administered radiolabeled albumin in the lung tissue and air space and improved the pulmonary response to surfactant treatment. There were no additional effects of TRH when given with corticosteroids on lung function or albumin leak. There were no changes in alveolar surfactant-saturated phosphatidylcholine pool sizes after any hormone treatment. The single significant effect of combined corticosteroid and TRH treatment was a fivefold increase in surfactant protein A in alveolar lavage fluid relative to all other groups.

Animals↗
PubMed1991

Nebulized vs. instilled exogenous surfactant in an adult lung injury model.

Three days after subcutaneous injection of N-nitroso-N-methylurethane (NNNMU) to induce lung injury, adult rabbits were mechanically ventilated and lung function was evaluated. Each animal then received either nebulized Survanta (Neb Surv), nebulized saline (Neb Saline), nebulized gas alone (Neb Gas), or tracheally instilled Survanta (Inst Surv). The ventilation efficiency index (VEI) value increased significantly compared with pretreatment values (P less than 0.01) over a 3-h treatment period for the Neb Surv animals, whereas VEI values for the other three groups decreased after treatment (P less than 0.05). Arterial PO2-to-fraction of inspired O2 ratios and dynamic compliance values significantly decreased after treatment for the Inst Surv group (P less than 0.05). Pressure-volume curves demonstrated a significantly greater volume at maximal pressure for the Neb Surv group compared with each of the other groups studied (P less than 0.01). The calculated quantity of surfactant recovered in lung tissue for the Neb Surv group was only 4.9 +/- 1.0 mg lipid/kg compared with 100 mg lipid/kg delivered to the Inst Surv group. Surfactant administered as an aerosol resulted in modest physiological improvements in this model of lung injury and was superior to the tracheal instillation technique.

Aerosols↗