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Biomedical subjects

F Chytil

Publications and source records attributed to F Chytil.

At least 19 recordsLinked to original sources
PubMed2000

Vitamin A status and postnatal dexamethasone treatment in bronchopulmonary dysplasia.

OBJECTIVE: Vitamin A (retinol) plays an important role in epithelial regeneration during recovery from lung injury in bronchopulmonary dysplasia (BPD). Dexamethasone is used in the postnatal treatment of very low birth weight (VLBW) neonates with BPD. To test the hypothesis that the vitamin A status is critical for the beneficial pulmonary response to dexamethasone, we performed a prospective cohort study in which we characterized the changes in plasma concentrations of vitamin A and retinol-binding protein (RBP) in response to dexamethasone, and correlated these changes with the pulmonary outcome. METHODS: VLBW neonates (birth weight <1350 g, gestational age <31 weeks, postnatal age >10 days), who had presumptive diagnosis of severe BPD and need for high ventilatory support (fraction of inspired oxygen >/=.6, mean airway pressure >/=7 cm H(2)O), were treated with a seven-day course of dexamethasone (.5 mg/kg/d x 2 days,.25 mg/kg/d x 2 days,.1 mg/kg/d x 3 days). Plasma concentrations of vitamin A and RBP were determined sequentially at baseline, and during and after dexamethasone treatment. Pulmonary response to dexamethasone was graded daily using a composite ventilation score. The changes in plasma vitamin A and RBP concentrations were compared between infants with a positive (beneficial) pulmonary response to dexamethasone and those with a negative response. RESULTS: Among 23 infants studied, 13 showed a positive pulmonary response to dexamethasone, as indicated by successful weaning from supplemental oxygen and mechanical ventilation, whereas 10 showed a negative response. A significant, yet short-term, increase in plasma concentrations of both vitamin A and RBP was observed in most infants treated with dexamethasone. The plasma vitamin A and RBP responses to dexamethasone tended to be higher in infants with a positive pulmonary response than in those with a negative response. Accounting for gender, a vitamin A response with each 10.0 microg/dL increment in plasma vitamin A concentration was associated with a 60% increase in the odds favoring a positive pulmonary response to dexamethasone. CONCLUSION: Postnatal dexamethasone treatment in VLBW neonates with BPD induces a significant, yet short-term, increase in plasma concentrations of both vitamin A and RBP. This increase probably results from endogenous mobilization of vitamin A from the liver. Our data suggest that the beneficial pulmonary response to dexamethasone in infants with BPD is influenced, at least in part, by the vitamin A status, and that gender plays a role in this response.vitamin A, dexamethasone, bronchopulmonary dysplasia.

Bronchopulmonary Dysplasia↗
PubMed1996

Retinoids in lung development.

The "retinoid revolution" has had considerable impact on research activity in the field of lung development. Postnatal lungs are very sensitive to dietary retinol (R) deprivation. The trachea and the bronchopulmonary tree in R-deficient animals show a striking change in morphology. The columnar epithelium undergoes keratinizing metaplasia, which is reversed when R is supplied. The fetal lung develops postnatally to become one of the most complex organs, characterized by 40 different cell types. The fetal lungs can accumulate retinyl esters. Before birth an unknown signal causes the lowering of these esters, which may be the source of retinoic acid (RA). The administration of glucocorticoids speeds up this process, which in turn is followed by acceleration of lung maturation, ending postnatally. It is not clear what role, if any, the cellular retinoid binding proteins play in this phenomenon. Fetal lung branching leading to the development of the alveolar tree is accelerated by RA, and so is the expression of some fetal genes coding for surfactant proteins and the enzymes that produce their lipid components. It is not clear whether RA influences the development of pulmonary epithelium by interacting directly with the epithelial cells or whether its effects require interaction with other cels like mesenchymal cells. Nuclear RA receptors are intimately involved in lung development. Despite the wealth of evidence on the effect of retinoids on lung development, the application of vitamin A to clinical work has been limited to prematurely delivered infants who have immature lungs. Here attempts are made, by improving their R status, to aid in the development and healing of lungs injured by oxygen therapy.

Animals↗
PubMed1996

Regulation of metabolism by retinoic acid and its nuclear receptors.

It is now well established that the pleiotropic effects of vitamin A-with the exception of the vision process-are mediated by its acid derivatives. Although all-trans retinoic acid has been known for some time to be an essential regulator for many important biological processes, critical roles for other acid derivatives have more recently emerged. The acid isoforms affect a large diversity of biological systems, including embryonal cells, lymphoid cells, and nerve and muscle cells, as well as essential developmental programs. Retinoic acid signals are mediated by specific nuclear receptors, the RARs and RXRs, which are part of a complex signaling network, allowing for receptor-receptor and receptor-DNA interaction, as well as for receptor interactions with other regulatory proteins. Dissection of the molecular mechanisms has been significantly advanced by the discovery of selective retinoids that in contrast to most natural retinoids activate only defined portions of the complex retinoid response. Some of these novel types of retinoids are also very promising candidates for the development of new therapeutics. Thus, the molecular analysis of the vitamin A derivative retinoic acid has opened new perspectives that form a connection between nutritional signals and the development of new therapeutic agents.

Cell Nucleus↗
PubMed1996

Safety aspects of vitamin A administration.

OBJECTIVE: To review longstanding experience in the safe use of vitamin A as therapeutic agent in prematurely born human neonates and more recently with young children infected with the respiratory syncytial virus (RSV). DESIGN: The studies reviewed were designed to intervene with vitamin A in the form of retinyl palmitate in human neonates and infants showing low levels of retinol in the blood. SETTING: Vanderbilt University School of Medicine. RESULTS: Evidence is presented that vitamin A can be administered safely to human neonates and infants without apparent acute toxic effects. CONCLUSION: A carefully designed mode of administration of vitamin A can improve a patient's vitamin A status as determined by the elevation of blood vitamin A levels which in turn may be beneficial in lowering the morbidity.

Humans↗
PubMed1995

Vitamin A status and airway infection in mechanically ventilated very-low-birth-weight neonates.

Vitamin A (retinol) plays an important role in immunity. Respiratory and enteral infections in children are associated with low serum vitamin A concentrations that improve during recovery. To test the hypothesis that airway infection in very-low-birth-weight (VLBW) neonates likewise may be associated with a change in vitamin A status, we examined 20 VLBW neonates (selection criteria: birth weight 700-1300 g, gestational age 26-30 weeks, need for supplemental oxygen and mechanical ventilation for > 72 hr after birth) who were enrolled in the control group of a randomized clinical trial of vitamin A supplementation reported earlier. We studied changes in weekly measurements of plasma concentrations of vitamin A and retinol-binding protein (RBP) during 4 weeks following enrollment in the trial (postnatal day 4) and compared changes between periods with and without airway infections. Seventeen infants had 22 episodes of documented airway infection. Staphylococcus epidermidis was the predominant organism. Plasma vitamin A concentrations decreased during 19 out of 22. With airway infection (mean change: -4.1 to -18.6 micrograms/dL), while they increased during 37 out of 58 periods without airway infection (mean change: -0.2 to +5.8 micrograms/dl; P < 0.001). The mean (+/- SD) plasma vitamin A concentrations before, during, 1 week after, and 2 weeks after an episode of airway infection were 20.9 +/- 8.3, 9.7 +/- 4.1, 12.8 +/- 8.9, and 16.2 +/- 7.2 micrograms/dL, respectively. The mean value during airway infection was significantly lower than those before and two weeks after airway infection (P < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Bacterial Infections↗
PubMed1995

Sequential evaluation of plasma retinol-binding protein response to vitamin A administration in very-low-birth-weight neonates.

Vitamin A (retinol) deficiency is associated with impaired healing from lung injury in very-low-birth-weight (VLBW) neonates susceptible to bronchopulmonary dysplasia (BPD). Vitamin A supplementation from birth may ameliorate this adverse outcome. We hypothesized that plasma retinol-binding protein (RBP) response to vitamin A administration, which provides a dynamic measure to vitamin A status, might be useful for early recognition of vitamin A deficiency in VLBW neonates at risk for BPD. We prospectively studied 20 VLBW neonates (inclusion criteria: birth weight < 1300 g, gestational age < 30 weeks, need for supplemental oxygen and mechanical ventilation for > 24 h after birth) who were eligible to receive vitamin A supplementation. In addition to sequential assessment of vitamin A status, we measured plasma RBP just before and 3 and 6 h after an intramuscular injection of vitamin A (2000 IU/kg retinyl palmitate) on Postnatal Days 1, 7, 15, 21, 29, and 43. The percentage increase in plasma RBP (delta-RBP) was calculated. A high plasma delta-RBP value ( > 8%) is indicative of vitamin A deficiency. Based on pulmonary outcome, the infants were divided into two groups: BPD (n = 12) and No BPD (n = 8). Mean vitamin A intake ranged from 1414 to 2114 IU/kg/day and did not differ between infant groups. Mean plasma vitamin A concentration increased from baseline levels on Postnatal Day 1 to levels within the desired range of 1.05-2.10 mumol/liter (30.0-60.0 micrograms/dl) during supplementation period in both infant groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Bronchopulmonary Dysplasia↗
PubMed1995

Mainstream and sidestream cigarette smoke exposure increases retinol in guinea pig lungs.

We have studied in guinea pigs the effects of cigarette smoke exposure on vitamin A (retinol) levels in plasma, lung, lung lavage, and liver. Smoke was generated from 1R3F cigarettes in a smoke exposure instrument designed by University of Kentucky Tobacco and Health Research Institute. Three-week-old male guinea pigs were exposed to mainstream, sidestream, or sham smoke, generated twice daily from three cigarettes for 6 weeks. In addition, some animals were kept as room controls for some time. After 6 weeks of smoke exposure, some animals were allowed to recover for 6 weeks without smoke. After 6 weeks of smoking, the plasma retinol levels were lower in both smoke exposed groups when compared to the values in the sham group. Furthermore, in comparison to the sham group, the mainstream and sidestream smoke exposed groups showed a 7.6- and 8.3-fold increase in the levels of lung retinol, respectively. After the 6-week recovery period, plasma retinol of both smoke-exposed groups reached the control levels. In contrast, withdrawal of smoking did not show such an effect on the lung retinol level in both mainstream or sidestream groups. Electronmicroscopy of the lungs showed deleterious alterations in the morphology of the lungs in both mainstream and sidestream groups. Although the mechanism(s) involved in the elevation of retinol content of the lung due to smoke exposure remains to be elucidated, it is of interest that elevation of retinol content and alteration of lung morphology occurred not only in the mainstream smoke exposed but also in the sidestream group.

Animals↗
PubMed1995

Safety and pharmacokinetics of vitamin A therapy for infants with respiratory syncytial virus infections.

Infants with respiratory syncytial virus infection have low serum vitamin A levels. We treated 21 respiratory syncytial virus-infected children with 12,500 to 25,000 IU of oral vitamin A. Vitamin A levels were normalized at 6 h, and none of the children experienced vitamin A toxicity or exacerbation of respiratory illness. Vitamin A treatment of previously healthy respiratory syncytial virus-infected infants at these doses is safe and well tolerated.

Humans↗
PubMed1994

Depletion of retinyl esters in the lungs coincides with lung prenatal morphological maturation.

Close to birth rat fetuses have lungs which are depleted in retinyl esters. Glucocorticoids administered to pregnant rats accelerate this process. We have investigated changes in fetal lung levels of retinol and retinyl palmitate and accompanying morphological changes after administration of dexamethasone to pregnant rats on day 18 of pregnancy. Here we show that this depletion temporarily coincides with prenatal morphological maturation of the lungs. The data presented support the idea that the maturational effect of glucocorticoids in the developing lungs is linked to vitamin A metabolism.

Animals↗
PubMed1994

Intramuscular versus enteral vitamin A supplementation in very low birth weight neonates.

We conducted a randomized trial in very low birth weight neonates (n = 51) to determine whether vitamin A supplementation by enteral administration would increase plasma vitamin A concentrations to the same degree as by intramuscular administration. Mean plasma vitamin A concentrations were significantly higher in the intramuscular-administration group than in the enteral-administration group by postnatal day 7; this effect persisted throughout the remainder of the trial. At the dosage used in this trial, vitamin A supplementation by the enteral route is not as effective as that by the intramuscular route in very low birth weight neonates.

Enteral Nutrition↗
PubMed1994

Serum vitamin A levels in respiratory syncytial virus infection.

Respiratory syncytial virus causes worldwide epidemics of respiratory disease. Of 23 children infected with respiratory syncytial virus, 65% had low serum concentrations of vitamin A during acute illness; these low values were associated with more severe illness. Vitamin A supplementation may have a role in the management of infection with respiratory syncytial virus.

Case-Control Studies↗
PubMed1994

Effect of maternal dexamethasone treatment on fetal lung vitamin A stores in the perinatal rat.

Vitamin A (retinol) is essential for normal differentiation of developing respiratory epithelium. Significant vitamin A storage occurs in the fetal lung near term (gestational day 21) in the perinatal rat, and the developing lung may be dependent on these local vitamin A stores during growth and differentiation. The growth and differentiation of fetal lungs can be enhanced by maternal treatment with glucocorticosteroids. We conducted this study in rats to determine the effect of maternal dexamethasone treatment on the lung stores of vitamin A in the offspring. Vitamin A-sufficient pregnant rats were given by intraperitoneal injection a single dose of either dexamethasone (300 micrograms) or 0.9% saline solution on gestational day 16. High performance liquid chromatography was used to measure concentrations of vitamin A and its esters, retinyl palmitate and stearate, in fetal and neonatal lungs and livers at times ranging from gestational day 19 through 21, and from postnatal day 1 through 7. The concentrations of vitamin A esters in the lungs of fetuses and newborn pups of the dexamethasone-treated animals were significantly lower than those of the control group in all determinations, the values ranging between 22 and 50% of controls. In contrast, the concentrations of vitamin A esters in the livers did not differ significantly between study groups. We conclude that a prompt, sustained, and selective decrease in the fetal lung stores of vitamin A appears to occur following maternal antenatal dexamethasone treatment. This decrease in the fetal lung vitamin A stores might be due to increased utilization of vitamin A associated with enhanced differentiation of the fetal lung induced by maternal dexamethasone treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

A retinoic acid response element from the rat CRBPI promoter is activated by an RAR/RXR heterodimer.

The expression of the rat cellular retinol binding protein I (rCRBPI) can be upregulated in vivo by retinoic acid (RA). Here we have analyzed the rCRBPI promoter region and compared it to the corresponding mouse sequence. We find that the CRBPI 5' flanking region has been highly conserved between rat and mouse, including a RA response element (RARE) approximately 1 kb upstream of the start of transcription. The RARE is of the direct repeat type with a two nucleotide spacer. Like other direct repeat RAREs, this response element is activated by RAR alpha and beta but not by RAR gamma 1. Furthermore, the rCRBPI-RARE is most effectively activated when both RAR and RXR are present. In addition RAR/RXR heterodimers are required for efficient binding to the rCRBPI-RARE, while RARs or RXR alone do not interact effectively with this response element. The rCRBPI gene is therefore most likely activated in vitro by a RAR/RXR heterodimer.

Animals↗