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Biomedical subjects

R D Zachman

Publications and source records attributed to R D Zachman.

At least 37 records · Page 2Linked to original sources

Some effects of vitamin A deficiency on the isolated rat lung alveolar type II cell.

Alveolar Type II cells were isolated from control and vitamin A deficient rats and allowed to form a monolayer in plastic dishes for 16-18 hours. The vitamin A content (retinol plus retinyl palmitate) of deficient cells was 50-75% less than in control cells on a per mg protein basis. Isolated Type II cells took up [3H]-retinol, synthesized [3H]-retinyl palmitate, and after 4 hours, 24% of the radioactivity in the Type II cells was [3H]-retinoic acid. Deficiency did not appear to alter retinoic acid synthesis. Phosphatidylcholine (PC) and disaturated phosphatidylcholine (DSPC) synthesis, were slightly less in deficient cells compared to control (95 and 85% respectively). In addition, 10(-6) M and 10(-5) M retinoic acid in the reaction media stimulated both PC and DSPC synthesis by 120-140% in control cells. The stimulating effect of retinoic acid was present in deficient cells as well, but less pronounced (120% with 10(-5) M). Vitamin A deficient Type II cells also had less basal levels of both tissue transglutaminase and epidermal transglutaminase activity than control cells.

Animals↗

Intramuscular relative dose response (RDR) determination of liver vitamin A stores in rats.

This study questioned whether the relative dose response (RDR) method to detect liver stores of vitamin A could be used by intramuscular administration of the vitamin. Vitamin A-deficient and reference rat serum retinol levels were determined by HPLC at zero time and then again 5 h after an intramuscular injection of 5.25 mumol/kg retinyl palmitate. The RDR percentage was calculated: [(A5-A0)/(A5)] x 100. The 5-h RDR was determined in 20 deficient and 16 reference diet rats and a clear relationship to liver retinyl palmitate concentration was demonstrated. At a liver retinyl palmitate concentration of less than 0.105 mumol/g, all RDR values were greater than 20%. When the liver retinyl palmitate was greater than 0.122 mumol/g the RDR was less than 20%. This study suggests that the intramuscular RDR is a valid tool for estimating liver retinyl palmitate in populations in which the oral RDR cannot be administered.

Animals↗

The effect of maternal ethanol ingestion on fetal vitamin A in the rat.

The effect of maternal ethanol ingestion on fetal tissue vitamin A was investigated. Pregnant rats were pair-fed control diets or diets containing 36% of energy as ethanol. After 17 or 21 d gestation, fetuses were removed and fetal and maternal tissues were analyzed by HPLC for retinol and retinyl palmitate. Ethanol consumption resulted in fewer fetuses per pregnancy, increased number of resorptions, and increased numbers of gross fetal abnormalities. In maternal tissues, ethanol consumption resulted in greater lung and kidney vitamin A concentrations. In the fetuses of ethanol-consuming pregnancies, free retinol in liver was higher at d 17. However, fetal liver palmitate levels and total retinyl palmitate in liver, lung, and kidney were lower in ethanol-fed rats at d 21 of gestation. Fetal lung retinyl palmitate concentrations were greater at both d 17 and d 21, and kidney levels were also greater at d 21. In conclusion, the ingestion of ethanol by pregnant rats is associated with a reduction in fetal liver vitamin A levels and an elevation in the levels of lung and kidney vitamin A, indicating possible altered vitamin A metabolism as a result of ethanol consumption.

Animals↗

Phosphatidylglycerol, lecithin/sphingomyelin ratio and respiratory distress syndrome in diabetic and non-diabetic pregnancies.

Samples of amniotic fluid from 514 non-diabetic and 69 diabetic patients were analyzed for phospholipid content. Results were correlated with incidence of respiratory distress syndrome (RDS) in the neonate. The incidence of RDS was 4.5% among diabetics and 5.3% among non-diabetics. In the presence of phosphatidylglycerol (PG), no infant developed RDS while in the absence of PG the incidence of RDS was 16.7% and 14.4%, respectively. In the presence of a mature lecithin/sphingomyelin (L/S) ratio the respective incidence of RDS was 1.6 and 1.8, while with an immature L/S ratio the incidence of RDS was 28.6% and 29%. The incidence of RDS after 37 weeks gestation was 0% among diabetics and 0.6% among non-diabetics. We conclude that amniotic fluid phospholipids are equally predictive of risk for RDS in diabetics as among non-diabetic patients. We suggest that in patients with accurate gestational dating, amniotic fluid analysis for phospholipids might not be necessary to establish fetal lung maturity.

Amniotic Fluid↗

Retinol (vitamin A) and the neonate: special problems of the human premature infant.

Retinol stores accumulate in fetal tissue during gestation. Hence, the premature infant faces extrauterine adaptation with less total reserves of retinol than does the term infant. Retinol-binding protein in serum is also lower in the premature infant population. The parenteral retinol supplementation frequently required for these infants has only recently become adequate by the finding of methods to avoid large losses of retinol onto intravenous tubing. Retinol is an essential vitamin for epithelial cell function; nearly 40% of lung cells are of epithelial origin. The premature infant's lung often is the initial site of difficulties during extrauterine adaptation, and respiratory system epithelial-cell damage and chronic lung disease frequently develop. Because these infants have associated low retinol reserves, retinol supplementation to help repair pulmonary injury is being considered. Some of these relationships are beginning to be clarified by basic research on the metabolism and function of retinol in lung.

Female↗

Lecithin:sphingomyelin ratio in the amniotic fluid of male and female fetuses.

The effect of fetal sex on the amniotic fluid lecithin:sphingomyelin (L:S) ratio was determined with a prospective, randomized, double-blind study designed to evaluate the effect of antenatal steroid administration on the incidence of neonatal respiratory distress syndrome. The immature L:S ratios of 183 single births to nondiabetic women were analyzed. L:S ratios increased with increasing gestational age. Regression lines of L:S versus gestational age suggested that male infants' L:S ratios were lower than females', although the differences were not statistically significant.

Amniotic Fluid↗

Effect of mode of delivery on incidence of respiratory distress syndrome.

The effect of route of delivery on incidence of respiratory distress syndrome (RDS) has been controversial. While some investigators have reported no difference in RDS rates in infants born by cesarean section as compared to vaginal delivery, others have shown a significant increase in risk for RDS among infants born by cesarean section. Data from the 297 patients comprising the placebo group in the recently completed collaborative study of antenatal steroid therapy in the prevention of neonatal RDS, were analyzed to determine the effect of mode of delivery on RDS. The results indicate that infants born by cesarean section without labor have a higher risk for neonatal RDS than infants born vaginally or by cesarean section after a trial of labor.

Cesarean Section↗

Effect of premature delivery on rat lung retinol (vitamin A) and retinyl ester stores.

Low plasma retinol (vitamin A) in premature infants has been associated with bronchopulmonary dysplasia. Also, retinol (vitamin A) deficiency is characterized by loss of cilia and squamous metaplasia of the respiratory tract, similar to the histological lesions of bronchopulmonary dysplasia of the premature infant. Recent work showed that the fetal rat lung retinyl palmitate stores were high preterm, but fell abruptly between 21 days of gestation and postpartum. This report extends this observation by showing that lung retinyl palmitate also decreases after cesarean section delivery preterm. Lung retinol and retinyl palmitate in the lungs of 21-day gestation fetuses delivered by cesarean section and stimulated to breath were compared to their in utero littermates. In utero lungs contained 2.2 +/- 0.14 micrograms/g dry weight retinol and 14.9 +/- 0.8 micrograms/g dry weight retinyl palmitate. Lungs from littermates that had been removed from the uterus and breathed on their own for 4 h had lower retinol (1.6 +/- 0.08 micrograms/g) and retinyl palmitate (11.3 +/- 0.4 micrograms/g; p less than 0.01). Fetal lung contains retinyl palmitate stores that are readily mobilized with delivery at term or preterm.

Animals↗

Effect of antenatal dexamethasone on neonatal leukocyte count.

The leukocyte count and differential white blood cell count during the first hour of life was determined in 164 neonates born of mothers receiving antenatal steroids and compared to 171 neonates of mothers randomly assigned to a placebo group. A leukemoid reaction (greater than 40,000 WBC/mm3) was seen only once each in the neonates born of placebo or steroid treated mothers. In addition, maternal steroid treatment had no general effect, except in a small subgroup of neonates born 3 to 7 days after the mother had been treated with 20 mg dexamethasone, where the total leukocyte and the absolute neutrophil counts were higher than the placebo group and other subgroups.

Analysis of Variance↗

Retinyl ester synthesis by isolated adult rabbit lung type II cells.

Type II alveolar cells were isolated from adult rabbit lungs and then cultured on monolayers for 16 hours. These cells were then covered with buffered medium containing [3H]-retinol. After 30-120 minutes incubation, the cells were extracted with Hexane: Ethanol and the hexane extract analyzed by HPLC. A linear synthesis of [3H]-retinyl palmitate with time of incubation was demonstrated.

Animals↗

Effect of oxygen exposure on newborn rabbit lung and liver retinol stores.

Newborn rabbit littermates were divided randomly and placed in environments of 21% oxygen or 70-75% oxygen for 68 hours. At that time lungs and liver were removed, and retinoids were measured by HPLC with methanol as the mobile phase. Lungs exposed to 70-75% oxygen had less retinol than controls, and livers of oxygen exposed animals had less retinyl palmitate and retinyl stearate than control animals. This effect of oxygen on newborn lung and liver retinol stores has not previously been reported.

Animals↗

The effect of antenatal dexamethasone on maternal and fetal retinol-binding protein.

Sixteen rhesus monkeys received 0.1 to 15 mg/kg of antenatal dexamethasone at 132 days' gestation; seven control animals received placebo. At 135 days' gestation they underwent cesarean section, and maternal and fetal serum was assayed for retinol-binding protein. Fetal and maternal concentrations of retinol-binding protein increased after dexamethasone (p less than 0.05) and there was a trend for fetal levels of retinol-binding protein to increase with increasing dosage (p less than 0.01). Whether the elevation of retinol-binding protein in response to antenatal dexamethasone is a desirable side effect is not clear at this time.

Animals↗

Retinyl ester synthesis by the isolated perfused-ventilated neonatal rabbit lung.

Retinyl ester is present in lung but it is unknown if retinyl ester synthesis occurs in that organ. In this study, [3H]-Retinol was perfused into the pulmonary artery of isolated-perfused-ventilated neonatal rabbit lungs. Alumina chromatography was used to separate retinol from retinyl ester in hexane extracts of lung tissue. [3H]-Retinyl ester synthesis did occur and was perfusion time and perfusate [3H]-retinol concentration dependent. Documentation of [3H] retinyl ester synthesis was also made by HPLC analysis of the retinyl ester fraction before and after methanolic KOH hydrolysis. Isolated lung clearly can synthesize retinyl ester.

Animals↗

Association between ruptured membranes, tocolytic therapy, and respiratory distress syndrome.

Two hundred ninety-seven patients from the placebo group of the National Institutes of Health Collaborative Study on Antenatal Steroid Therapy for prevention of respiratory distress syndrome were selected for analysis to investigate a possible association between premature rupture of the membranes, tocolytic therapy, and respiratory distress syndrome. Both premature rupture of the membranes and tocolytic therapy with isoxsuprine were individually associated with a lowered incidence of respiratory distress syndrome. However, when present together, their protective effect was not additive and resulted in a higher incidence of respiratory distress syndrome. It is suggested that the use of tocolytic therapy with beta-adrenergic agents be restricted to patients with intact membranes.

Amniotic Fluid↗

Relationship of vitamin A (retinol) status to lung disease in the preterm infant.

Plasma concentrations of retinol and retinol-binding protein were measured at birth in 91 preterm infants. In 64% of these babies retinol values were less than 20 micrograms/dl, suggestive of vitamin A deficiency. Forty-seven of these infants were observed with sequential measurements of retinol and retinol binding protein through 21 days of age. In babies with respiratory distress syndrome retinol values were similar to those in babies without respiratory distress syndrome. The retinol binding protein levels were lower on the third day of life in babies with respiratory distress syndrome. Babies who developed bronchopulmonary dysplasia had lower concentrations of retinol at birth (P less than 0.05) and on day 21 (P less than 0.05) than did babies who did not develop bronchopulmonary dysplasia, despite receiving recommended intakes of vitamin A. Many preterm infants are deficient in vitamin A at birth, and failure to correct this deficiency may contribute to the development of chronic lung disease.

Bronchopulmonary Dysplasia↗

Perinatal rat lung retinol (vitamin A) and retinyl palmitate.

The potential role for retinol (vitamin A alcohol) in the differentiation of the developing lung prompted this study in the perinatal rat. High performance liquid chromatography was used to separate, detect, and quantitate retinol and retinyl palmitate in lipid extracts of tissue and serum. Fetal and maternal blood showed the presence of retinol, whereas no retinyl palmitate was detected. On the other hand, fetal and postnatal lungs contained retinyl palmitate as well as retinol. Considerable changes in the content of lung retinyl palmitate were found during lung development. Fetal lungs (17-21 days of gestation) contained 2.3 +/- 0.36 micrograms/g wet weight (mean +/- SD) of retinyl palmitate and 0.14 +/- 0.05 micrograms/g of retinol. Lungs of pups (1-10 days old) contained much less retinyl palmitate, 0.63 +/- 0.20 micrograms/g, whereas the amount of retinol was the same as in fetal lungs. The surprisingly high content of retinyl palmitate in fetal lung and its depletion after birth may be functionally related to retinol action in the developing lung.

Animals↗

A decreased incidence of necrotizing enterocolitis after prenatal glucocorticoid therapy.

In a large multicentered, collaborative randomized and blinded trial utilizing antenatal corticosteroids, the goals included determining the effectiveness of these agents in accelerating lung maturation, as well as monitoring any short-term or long-term adverse effects of this treatment on the parturient, fetus, and/or infant. More than 100 specific items, pertaining to diagnoses, complications, and outcomes were recorded for the 696 mothers enrolled in the study and their 745 infants. A significantly decreased incidence of necrotizing enterocolitis (P = .002) was found in the infants treated with steroids. The possibility of accelerated intestinal maturation induced by antenatal maternal steroid therapy exists. This treatment regimen is particularly attractive as adverse aspects of steroid therapy at the dosage utilized have not been demonstrated.

Clinical Trials as Topic↗