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J Neu

Publications and source records attributed to J Neu.

At least 37 records · Page 2Linked to original sources

Ontogeny of prostaglandin E1 receptor binding in rat small intestine.

While prostaglandins of the E series are known to affect several small intestinal functions, their cellular mechanisms are poorly understood. The purposes of this study were to determine if there are developmental differences in the binding of PGE1, to the small intestinal enterocyte and if this binding may be affected by glucocorticoids, which are known to accelerate maturation of the small intestine. Small intestinal binding of prostaglandin E1 was significantly higher in adult rats when compared to postweaned (25-day-old) and preweaned (15- to 17-day-old) rats. Hydrocortisone administration for two days had no effect on the binding of prostaglandin E1 in either preweaned of adult rats. We conclude that a developmental change occurs in prostaglandin E1 binding to the plasma membrane of the rat small intestinal enterocyte during maturation. This binding is not affected by the administration of hydrocortisone.

Alprostadil↗

Localization and characterization of prostaglandin E1 receptors in rat small intestine.

While prostaglandins of the E series are known to affect several small intestinal functions, their cellular mechanisms are poorly understood. The purposes of our study were to determine whether receptors for PGE are present in rat small intestine and to locate and characterize the receptor binding in the subcellular fractions. Small intestinal binding of prostaglandin E1 was significantly higher than that of prostaglandin E2. Highest receptor binding for prostaglandin E1 was found in the plasma membrane fraction of isolated small intestinal enterocytes. Curvilinearity of prostaglandin E1 binding in plasma membranes upon Scatchard analysis indicated two receptor binding sites in rat small intestine. Competitive binding studies demonstrated that receptor binding was highest for prostaglandins of the E series. These studies are the first to demonstrate specific prostaglandin E1 receptors in different subcellular fractions of rat small intestine. We suggest that receptor binding of prostaglandin E may be an important initial step in the mechanism of prostaglandin-E-induced responses in the small intestine.

Animals↗

Factors associated with age of onset of necrotizing enterocolitis.

To investigate factors associated with risk and age of onset for necrotizing enterocolitis (NEC), a retrospective case-control review was performed of patients with NEC and control infants matched for birthweight and date of admission. NEC cases were defined by Bell staging criteria and were included if pneumatosis intestinalis, histologic confirmation, or a recognized complication of NEC was identified in association with clinical signs and symptoms. NEC was significantly related to birthweight and premature post-conceptional age. In contrast to control infants, patients with NEC had higher 5 minute Apgar scores, less significant respiratory disease, and more rapid feeding practices. Two distinct subgroups of patients with NEC based on postnatal age of onset were apparent. Patients with early onset NEC (21 days or less postnatal age) had less significant respiratory disease and were fed more rapidly than late onset patients. Late onset NEC (more than 21 days postnatal age) occurred frequently in convalescing, relatively well premature infants who were still, however, of preterm postconceptional age. Relatively well premature infants with minimal respiratory disease are still at risk for NEC. Advances in neonatal care and survival of very low birthweight infants may account for a shift in prevalence to older infants who are yet of preterm postconceptional age.

Age Factors↗

Determination of extracellular fluid volume using impedance measurements.

Currently, accurate determination of body fluid compartments depends on the sodium bromide method (NaBr), an invasive measurement requiring venipuncture with infusion of a foreign substance. Impedance (Z) measurements may provide a practical noninvasive alternative for estimating fluid compartments in sick, premature neonates. To validate the impedance method, we compared it with the NaBr technique in nine anesthetized rabbits. Electrodes were placed for impedance measurement. Vascular catheters were inserted into the femoral artery and vein. Baseline impedance data were collected at 1.0 kHz and blood samples were drawn for NaBr standard assay. Using conventional assay techniques for determination of extracellular fluid volume (ECFV), we correlated NaBr data with impedance measurements. A linear relationship between ECFV by NaBr assay and the previously developed impedance equation rho L2/Z1.0 was established using regression analysis. A correlation value of r = .95 was obtained. These data suggest the potential for impedance to estimate ECFV.

Animals↗

Changes in phospholipid and cholesterol concentrations of the rat microvillus membrane during maturation.

We studied the cholesterol and phospholipid content and the cholesterol-to-phospholipid molar ratio of the small intestinal microvillus membrane in fetal, weanling, and adult rats. We also investigated the effect of glucocorticoid administration on these lipids and the ontogeny of 1,2-diglycerol-CDP choline phosphocholine transferase (PCT). Cholesterol and phospholipid concentrations decreased with maturation, phospholipids declining more than cholesterol. Thus, the cholesterol-to-phospholipid molar ratio rose with maturation. A similar decline was seen with PCT activity. Glucocorticoid treatment had no effect on cholesterol, phospholipids, or PCT. However, the maturational increase in the cholesterol-to-phospholipid molar ratio was blunted by glucocorticoid administration in the weanling and adult rats.

Age Factors↗

Prostaglandin concentrations in human milk.

Concentrations of prostaglandin E2, prostaglandin F2 alpha (PGF2 alpha), and its metabolite 13,14-dihydro-15-keto prostaglandin F2 alpha (DHKF2 alpha) were measured in human milk at three different stages of lactation in mothers of premature and term infants. Before radioimmunoassay, our samples were purified by solid-phase extraction with C18Sep-Pak cartridges and reverse-phase high-performance liquid chromatography. When concentrations of the three prostaglandins were compared in the milk of mothers delivering prematurely and at term, very low concentrations were measured and no differences were observed. Concentrations of prostaglandins also remained essentially the same at the various stages of lactation. However, the mean ratio of DHKF2 alpha to PGF2 alpha was higher in samples from mothers who delivered early than in samples from those who delivered at term. These ratios were comparable to those reported in the literature for human plasma. The functional significance of these compounds in human milk remains undetermined.

Adult↗

Microsomal arachidonate bioconversion in rat small intestine during maturation.

This study was designed to compare prostaglandin (PG)-synthesizing activity in rat small intestinal microsomes in the 1st, 3rd, and 6th weeks of life and at maturity (greater than 100 days). When an incubation system was used containing 2 mg microsomal protein, 0.5 mM (-)-epinephrine and 1 mM reduced glutathione, the highest PG-synthesizing activity was achieved by incubating 0.157 mM 1-(14)C-arachidonate (specific activity 2.6 X 10(6) dpm/mumol) at 37 degrees C for 5 min. The labeled metabolites were extracted and then separated with high performance liquid chromatography. The four PGs analyzed were 6-keto-prostaglandin F1 alpha (6-keto-PGF1 alpha), thromboxane B2, prostaglandin F2 alpha and prostaglandin E2. Enzymatic activity for the synthesis of 6-keto-PGF1 alpha was much higher than that for the other PGs. A significant difference was observed for the bioconversion from arachidonate to 6-keto-PGF1 alpha and total PGs among the four age groups of rats. The postweanling groups (week 6 and adult) showed significantly higher enzymatic activities for the syntheses of 6-keto-PGF1 alpha and total PGs than did the preweanling groups (weeks 1 and 3).

6-Ketoprostaglandin F1 alpha↗

Maturation of antioxidant enzymes in rat small intestine: lack of glucocorticoid stimulation.

We report in detail the ontogeny and the response of antioxidant enzymes to glucocorticoids in the rat small intestine. Pregnant rats in the treatment group received four injections of dexamethasone starting on days 18, 19, or 20 of gestation; fetuses were killed 2 days later. Control rats were injected with 0.9% saline solution. Postnatal rats reaching 14, 19, and 104 days of age received four injections of hydrocortisone and were killed 2 days later. Age-matched controls were injected with 0.9% saline solution. The activities of xanthine oxidase, superoxide dismutase, and catalase were measured in small intestines from fetal (20 and 21 days gestation), newborn, and older (aged 16, 21, and 106 days) rats. Xanthine oxidase rose with maturation; the major increase occurred on postnatal day 21. Catalase and superoxide dismutase rose minimally during intrauterine life. On day 16 postpartum, catalase and superoxide dismutase values were 160% and 60%, respectively, higher than at birth. Glucocorticoid administration stimulated maltase and sucrase activities, but had no effect on the antioxidant enzymes or xanthine oxidase.

Animals↗

Alterations in piglet small intestine after cholesterol deprivation.

Mammalian cells require cholesterol for normal cell function. This requirement can be fulfilled by endogenous biosynthesis or by extracellular supplementation. Infants fed with human milk receive greater quantities of cholesterol than those fed commercial formulas. Whether this lack of cholesterol in commercial formulas poses a threat to normal neonatal cell function is not known. We compared small intestinal microvillus membrane fluidity, hydrolase activities, protein concentration, permeability to nonabsorbable markers, and weight gain in neonatal piglets receiving restricted intake of isocaloric formulas containing either normal amounts of cholesterol (145 mg/dl) or very low levels of cholesterol (less than 2 mg/dl). Using the fluorescent probe, diphenylhexatriene, and fluorescence polarization, microvillus membranes from cholesterol deprived piglets demonstrated higher fluidities than did microvillus membranes from animals fed normal concentrations of cholesterol. Cholesterol-deprived animals, even though their caloric intake was similar to cholesterol-fed animals, demonstrated a net weight loss per animal whereas the cholesterol-fed animals demonstrated a weight gain. These results demonstrate that in a pig model on a restricted intake, cholesterol deprivation alters the biophysical properties of the microvillus membrane.

Animals↗

Low levels of prostaglandins in human milk after purification by high performance liquid chromatography.

In order to validate methodology for quantifying arachidonic acid metabolites in human milk, we measured five prostaglandins (PGs) using radioimmunoassay (RIA): PGE2, PGF2 alpha, thromboxane B2 (TXB2), 6-keto-PGF1 alpha (6KF1 alpha) and 13,14-dihydro-15-keto-PGF2 alpha (DHKF2 alpha). RIA was performed after extraction with C18 Sep-Pak cartridge and/or further purification with reverse-phase high performance liquid chromatography (rp-HPLC). Recovery was monitored throughout the purification steps. Confirming findings of previously reported studies, we found PGE and the PGF2 alpha metabolite, DHKF2 alpha to be the major PGs in extracted human milk. After HPLC purification, however, no predominant PG was found, and the PG levels, especially those of PGE2 and DHKF2 alpha, were considerably lower than levels in the extracted sample. A noteworthy finding was the presence of immunoreactive substances in HPLC fractions not within the area of the PG peak; this suggests that the decreased levels of PGs in human milk measured by RIA after rp-HPLC are due to the elimination of the nonspecific immunoreactive materials present in the sample.

6-Ketoprostaglandin F1 alpha↗

A comparative evaluation of three neonatal ventilators.

The comparative reliability of three neonatal ventilators was evaluated using an infant model lung to simulate airway resistance and lung compliance. The ventilators tested were the Bourns BP200, the Healthdyne TI-11, and a positive-pressure ventilator called the PREEMIE (not commercially manufactured) used in several neonatal units in the Milwaukee area. The Bourns and Healthdyne ventilators generated similar airway and alveolar pressures while the PREEMIE produced alveolar, peak inspiratory, and positive end-expiratory pressures that exceeded the respective ventilator pressure settings by up to 11 cm H2O. The simple method described here should be generally useful for the evaluation of neonatal ventilator output.

Airway Resistance↗

Glucocorticoid-mediated alteration of fluidity of brush border membrane in rat small intestine.

The normal biophysical properties of the maturing mammalian enterocyte membrane are poorly understood. While the effects of glucocorticoids on maturation of intestinal enzyme function has been intensively investigated, their effects on membrane biophysical properties are not known. We used 1,6-diphenyl-1,3,5-hexatriene as a probe in fluorescence anisotropy studies to determine the fluidity of rat brush border membrane. Maturational changes and the effects of glucocorticoids administered antenatally or postnatally were determined. Fluorescence anisotropy values for 1,6-diphenyl-1,3,5-hexatriene in mature brush border membranes were higher than those values in membranes obtained from younger animals reflecting a less fluid membrane. Glucocorticoids administered to suckling rats increased the anisotropy values of 1,6-diphenyl-1,3,5-hexatriene in the membranes compared to saline-administered littermates. The anisotropy of intestinal brush border membrane was also increased in fetal rats whose mothers received dexamethasone. These alterations may relate to protein-binding properties and permeability characteristics of the enterocyte membrane.

Animals↗

Comparative effects of glucocorticoids and prostaglandins on small intestine of infant rats.

Previous studies have suggested similarities between the effects of exogenously administered glucocorticoids and prostaglandins in the developing rat small intestine. In this study the effects of exogenously administered glucocorticoids and prostaglandins were compared. In addition, the effects of prostaglandins in adrenalectomized rats were evaluated. Members of both classes of compounds stimulate small intestinal disaccharidase activities, and increase RNA to DNA ratio and brush border membrane protein synthesis. Hydrocortisone accelerates enterocyte turnover, whereas prostacyclin does not. Enteral administration of 16,16-dimethyl prostaglandin E2 stimulates disaccharidase activities in intact as well as sham-operated and adrenalectomized animals. The data suggest that certain prostaglandins may play a role in small intestinal metabolism which is similar to that of the glucocorticoids but is independent of the adrenal-intestinal axis.

16,16-Dimethylprostaglandin E2↗

Increased risk of gastrointestinal perforations in neonates mechanically ventilated with either face mask or nasal prongs.

Twenty cases of gastrointestinal perforations not associated with necrotizing enterocolitis or a bowel obstruction (GPNN) were reviewed. Fifteen infants suffered perforations during cycle ventilation. Perforations were localized in the stomach, duodenum, ileum, and jejunum. To determine if the type of mechanical ventilation used (ie, face mask, nasal prongs, or endotracheal tube) was associated with GPNN, a matched case-control analysis was performed. Case and control infants were matched by means of Apgar scores, gestational age, and length of time on ventilatory support. The Mantel-Haenszel estimate for estimating odds-ratios was used to determine that infants ventilated with nasal prongs or face mask were more likely to develop a gastrointestinal perforation than control infants ventilated with endotracheal tubes (odds-ratio greater than or equal to 29.6). This risk was associated with both upper gastrointestinal perforations (odds-ratio greater than or equal to 21.0) and lower gastrointestinal perforations (odds-ratio greater than or equal to 15.3). Routine use of mechanical ventilation with either nasal prongs or face mask appears to be associated with an unacceptable risk of gastrointestinal perforations in sick neonates.

Duodenal Diseases↗

Long-term high-frequency jet ventilation in neonates.

High-frequency jet ventilation (HFJV) markedly improved the ventilatory status of 2 neonates with severe respiratory failure refractory to conventional mechanical ventilatory support. However, after approximately 1 wk of HFJV, both patients expired from causes not directly related to ventilatory compromise. Autopsy showed no gross alterations in tracheal or bronchial mucosa but did reveal microscopic lesions which could be attributable to HFJV.

Bronchi↗