Biomedical subjects

I H Gewolb

Publications and source records attributed to I H Gewolb.

At least 37 records · Page 2Linked to original sources

PubMed1993

High glucose causes delayed fetal lung maturation as measured by fluorescence anisotropy.

Fluorescence anisotropy has been used to estimate the microviscosity of the surfactant phospholipid bilayer and no predict fetal lung maturity in human amniotic fluid; its usefulness in in vitro systems has been recently demonstrated. To investigate the effect of high glucose on lung development, anisotropy measurements were performed on 20-day fetal rat lung explant homogenates and culture media after culture for 48 hours in medium containing final concentrations of 10, 50, and 100mM glucose. Anisotropy of lung tissue cultured in 100mM glucose was significantly increased when compared to those cultured in 10mM glucose (p < .01). After 48 hours, the media from samples grown in 100mM glucose had significantly higher anisotropy (.2210 +/- .0031) than did media from explants grown in 50mM glucose (.2027 +/- .0079; p < .05), or in 10mM glucose (.1886 +/- .0046; p < .001). Relative fluorescence intensity of explants grown in 100mM glucose was 74.4 +/- 5.7% of those grown in 10mM glucose (p < .01). Fluorescence intensity of media was also decreased by 15-30% under higher glucose considerations (p < .05). These data suggest that surfactant synthesized and secreted under high glucose conditions, such as exist in the infant of the diabetic gestation, may have qualitative as well as quantitative changes.

Animals↗

PubMed1993

Reversal of lung maturational delay in the fetus of the diabetic rat using triiodothyronine or dexamethasone.

Administration of glucocorticoids and thyroid hormone can accelerate fetal lung development. To investigate whether the delayed fetal lung maturation seen in the diabetic rat gestation could be reversed by dexamethasone (DEX) or triiodothyronine (T3), control and streptozotocin-diabetic dams were injected daily from day 18 of gestation with either saline, 0.5 mg/kg DEX, or 1 mg/kg T3 until sacrifice on day 21 or day 22. While DEX did not change glucose levels in diabetic animals, T3 resulted in a slight reduction in both maternal (474 +/- 25 vs. 539 +/- 17 mg%; p < 0.07) and fetal (354 +/- 43 vs. 404 +/- 26 mg%; p < 0.05) serum glucose concentrations. DEX therapy exaggerated the reduction in body and lung weight seen in fetuses of streptozotocin-diabetic dams. Fetal lung phosphatidylcholine and disaturated phosphatidylcholine levels were significantly reduced in saline-treated diabetic animals as compared with controls. However, fetuses of T3- or DEX-treated diabetic rats had significantly increased lung phosphatidylcholine and disaturated phosphatidylcholine levels were significantly reduced in saline-treated diabetic animals as compared with controls. However, fetuses of T3- or DEX-treated diabetic rats had significantly increased lung phosphatidylcholine and disaturated phosphatidylcholine levels as compared with fetuses of untreated diabetic rats; these data suggest that maternal DEX or T3 therapy reverses the delayed fetal lung maturation seen in the diabetic rat gestation. Since glucocorticoids can exacerbate maternal diabetes, treatment with thyroid hormone may be more appropriate, although risks must be weighed against potential benefits.

Animals↗

PubMed1992

The relationship between rhythmic swallowing and breathing during suckle feeding in term neonates.

Little is known of the development of efficient coordination between suckle feeding and breathing in human infants. To establish baseline data, we recorded breathing and swallowing activity during bottle feeds in 23 infants at 14-48 h postnatal age. Most swallows (overall mean 68%) were organized into runs, with intervals starting at 0.6-0.8 s and slowing to 1-1.3 s after 30-40 s. The proportion of run swallows to total swallows increased significantly with age. Swallow intervals were regular (coefficient of variation = 18-38%) compared with breathing (coefficient of variation = 50%). Both breathing rate and tidal volume were significantly reduced by the onset of suckle feeding, and the pattern of respiratory airflow became markedly irregular. Mild transient desaturation was common, but was not accompanied by changes in heart rate. Swallows could occur in all phases of breathing. Overall, equal numbers of swallows were preceded by expiration and inspiration, but twice as many were followed by expiration compared with inspiration. Swallows were classified by the respiratory phases both preceding and following the swallow. Swallows occurred in all possible classifications in each of the infants studied. The incidence of the most frequent classification (inspiration-swallow-expiration), was 24% overall (individual range 5-50%). The phase relation between swallows and breaths changed frequently but showed occasional short periods of stability during which the breathing became regular and tidal volume increased. We conclude that at less than 48 h the normal infant has little coordination between swallowing and breathing rhythms and maintains rhythmic swallowing at the expense of eupnea.

Bottle Feeding↗

PubMed1986

Fetal and maternal corticosterone and corticosteroid binding globulin in the diabetic rat gestation.

Delayed fetal lung development is a feature of the diabetic pregnancy. Since fetal glucocorticoids are important in the regulation of lung maturation, we measured corticosterone and corticosteroid-binding globulin binding capacity in streptozotocin-diabetic pregnant rats and their fetuses. Previous studies have demonstrated delayed fetal lung maturation in this animal model. In control fetuses, total corticosterone concentration increased through day 20 of gestation, then declined until day 22 (term). The unbound steroid, which accounted for 5-10% of the total, increased approximately 3-fold from day 18 to term. Corticosteroid-binding globulin binding capacity peaked on day 19 after which it decreased. Maternal total and unbound corticosterone levels and corticosteroid-binding globulin binding capacity remained relatively constant throughout the final week of normal gestation. When compared to controls, fetuses from diabetic pregnancies had significantly lower total corticosterone from day 19 through 22. Corticosteroid-binding globulin binding capacity was also significantly decreased in these fetuses for the last 4 days of gestation. Similar differences were noted in maternal samples. However, no significant differences in unbound, biologically active, corticosterone were seen when diabetic and control groups were compared. Thus, delayed fetal lung maturation observed in fetuses of streptozotocin-diabetic rats is associated with a decrease in total circulating corticosteroid levels late in gestation. However, since unbound corticosteroid levels were similar in fetuses of control and diabetic animals, it is likely that other mechanisms may be responsible for the observed delay in lung development in fetuses of diabetic pregnancies.

Animals↗

PubMed1986

Fine structural abnormalities of the placenta in diabetic rats.

In the streptozocin-induced diabetic rat, the placenta is larger and the fetus is smaller than normal. To study cellular differences that might contribute to the size and functional disparity between diabetic and control placentas, a light- and electron-microscopic analysis was performed on 14-, 18-, and 22-day (term) control and diabetic placentas. Diabetic placentas, especially later in gestation, were marked by the presence of large numbers of glycogen-distended cells in the basal zone. Within the placental labyrinth, the trophoblastic layers of the interhemal membrane were significantly thicker in the diabetic placentas on days 18 and 22, and large accumulations of liid droplets were present, especially in the inner two trophoblastic layers. In normal placentas there is a marked thinning of the placental barrier in the labyrinth by day 22 of gestation, making the thickness of the labyrinthine layers in age-matched diabetic placentas even more impressive. Finally, the labyrinth of 22-day diabetic placentas contained more glycogen and rough endoplasmic reticulum in the inner trophoblastic layer, a feature that is found in less-mature (18-day) control placentas. Thus, the diabetic placentas have a number of features that are consistent with functional immaturity/dysmaturity. Cytologic evidence confirms the presence of increased glycogen and lipid reserves in both the junctional zone and the cellular area between maternal and fetal blood.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1985

Delayed pulmonary maturation in the fetus of the streptozotocin-diabetic rat.

Pulmonary maturation was studied in fetuses in streptozotocin-diabetic rats on the final four days of gestation. Diabetes was induced prior to conception by the intravenous injection of streptozotocin. Fetuses were hyperglycemic but did not manifest hyperinsulinemia. Whole lung total phospholipid, phosphatidylcholine, and disaturated phosphatidylcholine were significantly decreased in the diabetic group on day 21 (term = 22 days), but not prior to or after that point in gestation. Morphologic analysis also revealed a decreased number of type II cells and lamellar bodies per alveolar lining cell in the diabetic group only on day 21, coincident with the changes in phospholipid analysis. Activities of enzymes involved in fetal pulmonary phospholipid synthesis were measured to see if differences could account for the observed developmental delay. No significant differences between diabetic and control lungs were noted in any of the enzymes studied from days 20-22, with the exception of an increase in cholinephosphate cytidylyltransferase activity in the diabetic fetuses on day 22. Immaturity in both biochemical and morphologic indices of lung development was present at a specific time late in the diabetic rat gestation. This maturational delay could not be accounted for by changes in the activities of enzymes involved in phospholipid synthesis. The fetus of the streptozotocin-diabetic rat provides a useful model to study the effects of hyperglycemia on fetal lung development.

Animals↗

PubMed1985

Creatine kinase brain isoenzyme: relationship of cerebrospinal fluid concentration to the neurologic condition of newborns and cellular localization in the human brain.

Immunocytochemical study of human brain showed creatine kinase brain isoenzyme (CKBB) present in both neurons and astrocytes. Because creatine kinase brain isoenzyme is an intracellular enzyme that might be released with brain injury, its concentration in the CSF of newborns was measured using a radioimmunoassay. Infants who suffered a documented neurologic insult (a cerebroventricular hemorrhage or a CNS infection) were found to have a greater mean CSF creatine kinase brain isoenzyme concentration than those without a history of neurologic insult. Infants with a high concentration had a poor short-term outcome (death or neurologic abnormality when discharged) more frequently than did those with a lower concentration. Infants with a grade 3 or 4 cerebroventricular hemorrhage had a higher mean concentration than did those with a grade 1 or 2 hemorrhage. These data are consistent with the hypothesis that CSF creatine kinase brain isoenzyme is a metabolic indicator of brain damage in newborns.

Astrocytes↗

PubMed1984

Glucocorticoid-thyroid hormone interactions in fetal rat lung.

Previous studies have shown that triiodothyronine (T3) enhances the effect of dexamethasone on phosphatidylcholine (PC) synthesis in organ cultures of fetal rat lung. The aim of this study was to investigate whether similar interactions occurred in vivo and to explore possible mechanisms for this phenomenon. Injection of 7.0 mg/kg T3 into pregnant rats on d 18 and 19 of gestation resulted in a mean fetal serum T3 level of 2380 ng/dl on d 20 (control, 84 ng/dl) and in maximal (34%) stimulation of choline incorporation into PC. Injection of 1.0 mg/kg betamethasone using the same protocol as for T3 resulted in maximal stimulation of 33% and administration of both hormones together produced a 69% increase, an additive affect. The percentage of PC that was disaturated was increased with betamethasone, but decreased with T3. Betamethasone treatment resulted in an increase in the whole lung disaturated PC content, but treatment with T3 did not. Betamethasone administration also increased fetal serum T3 levels, but T3 injection did not produce elevated fetal serum corticosterone levels. Injection of T3 in vivo, or exposure of explants of 18-d fetal lung to 100 nm T3 for up to 48 h did not result in an increase in cytoplasmic glucocorticoid binding or nuclear translocation of the receptor steroid complex. Exposure of explants to glucocorticoid or T3 in vivo or in culture (dexamethasone, 100 nM and T3, 100 nM; for 48 h) resulted in a significant increase in the activity of cholinephosphate cytidylyltransferase, an enzyme in the choline incorporation pathway of PC synthesis.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1983

Placental growth and glycogen metabolism in streptozotocin diabetic rats.

Placental glycogen metabolism was investigated in rat pregnancies complicated by streptozotocin-induced diabetes mellitus. Both diabetic and control placentas had increasing glycogen concentration from day 14 to day 16, after which glycogen concentration declined rapidly. The diabetic placentas had significantly elevated glycogen concentration when compared to controls from day 16 through term (day 22). Near term, when control glycogen content fell close to zero, the diabetic placentas still had appreciable glycogen levels. Total phosphorylase activity in the diabetic placentas was significantly higher than control values from day 16-22. Phosphorylase A activity, however, was lower in the diabetic placentas late in gestation, corresponding to the increased glycogen concentration seen at that time. Diabetic placentas had increased total synthase activity on the final 3 days of gestation, although synthase A activity was lower than corresponding control values. The placentas in this model are markedly increased in size late in gestation. No difference in protein concentration or protein/DNA ratio was noted. Total DNA content per placenta was significantly increased in the diabetic placentas after day 16 when compared to controls. Placental DNA in the diabetics continued to increase until day 18-19 of gestation, whereas DNA content in control placentas remained constant after day 16. Thus, the diabetic placentas apparently continue the process of DNA replication after DNA synthesis is complete in the controls.

Animals↗

PubMed1983

Prenatal diagnosis of a human pseudoacardiac anomaly.

A unique case is presented of dichorionic-diamnionic twins, one of which contained a primitive heart arrested at an early stage of development and which resembled in many other respects a classic case of acardia. Lack of vascular anastomoses, the dichorionic nature of the twins, and ultrasonic evidence of independent heart rates suggest that the primary pathogenesis in acardia may be cardiac dysmorphogenesis rather than reversal of vascular flow. Ultrasonography and fetal echocardiography proved useful in delineating many of the features of the amorphous twin before delivery.

Abnormalities, Multiple↗

PubMed1982

Delay in pulmonary glycogen degradation in fetuses of streptozotocin diabetic rats.

The developmental profile of pulmonary glycogen was investigated in fetuses of rats made diabetic before conception with the injection of 40 mg/kg streptozotocin. Lungs of control litters showed increasing pulmonary glycogen concentration from day 16-20, followed by significant decline by term (= 22 days). In contrast, the diabetic litters, which had pulmonary glycogen concentration equal to controls until day 20, showed significantly higher glycogen values (P less than 0.01) on days 21 and 22, consistent with a delay in glycogen degradation. This coincided with the finding of decreased amounts of fetal pulmonary phosphatidylcholine and disaturated phosphatidylcholine on day 21 of the diabetic gestation (P less than 0.05), but not before that time. Pulmonary glycogen phosphorylase A activity was significantly decreased in the diabetic litters on the final days of gestation, at the same time that the delay in glycogen breakdown became evident. Pulmonary glycogen synthase activity did not differ in the control and diabetic fetuses. The delay in pulmonary glycogen degradation seen in the fetus of the diabetic gestation is thus temporally related to the delay in lung maturation seen in this model and may be secondary to a decrease in the activity of the glycogenolytic enzyme phosphorylase A. Decreased availability of pulmonary glycogen stores for surfactant synthesis may be important in elucidating the mechanism of the delayed pulmonic maturation seen in fetuses of diabetic pregnancies.

Animals↗

PubMed1981

Horizontal nonparenteral spread of hepatitis B among children.

Two families with an unusually high incidence of hepatitis B infection (15 of 21 persons) were investigated over an 18-month period. Serologic evidence of past or present infection--hepatitis B surface antigen (HBsAg), antibody to hepatitis B surface antigen (anti-HBs), or antibody to hepatitis B core antigen (anti-HBc)--was found in 11 of the 12 members of one family, four of whom were chronic HBsAg carriers, and in four of nine members of a contact family. Anti-HBc was the only serologic marker of infection in five persons. Histocompatibility leukocyte antigen (HLA) typing failed to show an association between carriage of HBsAg and specific HLA markers. Chewing gum was a potential vehicle as HBsAg was detected in gum samples from three of four children who were chronic HBsAg carriers. Horizontal, nonparenteral transmission of hepatitis B virus probably accounted for the clustering of infection in these families, especially via the exchange among children of objects contaminated with oral secretions.

Adolescent↗

PubMed1979

Thymus size and its relationship to the respiratory distress syndrome.

Thymic size can be affected by both exogenous and endogenous glucocorticoids. The risk of respiratory distress syndrome is reduced after maternal steroid administration. To find whether fetal lung maturity correlates with size of the thymus, the cardiothymic:thoracic ratio was measured in 167 newborn infants with and without RDS. Mean CT/T was significantly greater (0.40 vs 0.35; P less than 0.001) in those babies with RDS. This relation was independent of gestational age, although an increase in CT/T with advancing gestational age was shown. Prepartum maternal steroid administration did not result in significant involution of the cardiothymic shadow when compared with control infants with and without RDS. The CT/T may be of use in predicting which premature babies are more likely to develop RDS.

Female↗

PubMed1977

Amniotic fluid cortisol in high-risk human pregnancies.

Amniotic fluid cortisol (AFC) levels were measured in 76 normal and 67 high-risk human pregnancies. When compared to normal gestations, diabetic pregnancies were found to be associated with lower AFC levels, while toxemic, early Rh-sensitized, and other stressed pregnancies had higher mean cortisol values. Serially followed normal and high-risk pregnancies showed a progressive rise in AFC with increasing gestational age. Significant correlation between AFC concentrations and lecithin/sphingomyelin (L/S) ratios was noted in normal, diabetic, and toxemic gestations. These results are concordant with the hypothesis that cortisol may be involved in fetal lung development.

Amniotic Fluid↗

PubMed1977

Amniotic fluid cortisol as an index of fetal lung maturity.

Amniotic fluid cortisol concentration was compared with lecithin/sphingomyelin ratio, gestational age, and eventual birth-weight in a large series of normal and high-risk human pregnancies in an effort to determine whether cortisol could be used as a reliable indicator of fetal maturity. It appears that when used alone amniotic fluid cortisol is of limited clinical value as an antepartum predictor of fetal respiratory status because of unacceptable percentages of false positive and false negative predictions. Whether amniotic fluid cortisol can be used as an adjunct in the evaluation of high-risk pregnancies with "transitional" L/S ratios remains to be explored.

Amniotic Fluid↗

PubMed1976

Unconjugated cortisol in human amniotic fluid: relationship to lecithin/sphingomyelin ratio.

A specific and thoroughly validated competitive protein binding radioassay has been developed for the measurement of unconjugated cortisol in human amniotic fluid. Cortisol levels rose throughout normal gestation from 8.6 +/- 0.8 ng/ml at less than 20 weeks to 19.8 +/- 1.5 ng/ml at 30-40 weeks. Levels were significantly higher in amniotic fluid samples having mature lecithin/sphingomyelin (L/S) ratios (greater than 2), and good correlation with individual cortisol values was obtained (r = 0.79; P less than 0.001). These results support the hypothesis that cortisol plays a role in fetal lung maturation.

Amniotic Fluid↗

PubMedDate not supplied

Glucose decreases steady state mRNA content of hydrophobic surfactant proteins B and C in fetal rat lung explants.

The streptozotocin-induced diabetic (STZ-DB) rat model is associated with fetal hyperglycemia, but with low to normal plasma insulin concentration. Because surfactant protein (SP) mRNA content in fetal rat lung is decreased in STZ-DB pregnancy, we investigated the effect of increasing concentrations of glucose on SP gene expression in lung organ cultures. SP mRNA content (SP-A, SP-B, SP-C) was assessed by Northern blot analysis in fetal day 20 lung explants (term = 22 days) cultured for 44 hours in medium containing 10, 25, 50, or 100 mM glucose. Our findings were (1) No consistent alteration in SP-A mRNA content was observed at different glucose concentrations (P > .05); (2) SP-B and SP-C mRNA content were reduced in a dose-dependent manner when glucose concentration was increased from 10 mM to 100 mM. The mRNA content, compared to 10 mM glucose, decreased to 50-60% at 25 mM glucose, to 20-25% at 50 mM glucose, and to lower than 10% at 100 mM glucose (P < .01). These findings indicate that the decrease in SP-B and SP-C mRNA in fetuses of STZ-DB rats may be, in part, due to a direct effect of hyperglycemia, whereas the decrease in SP-A mRNA content in STZ-DB rats appears to be due to other effects of diabetes in pregnancy.

Animals↗

PubMedDate not supplied

Role of glutamine in bacterial transcytosis and epithelial cell injury.

BACKGROUND: L-Glutamine is the principal energy source for small intestinal enterocytes. Diminution of intestinal function, mucosal atrophy, and increased bacterial translocation have been noted during total parenteral nutrition (TPN). In a rat model of glutamine starvation, we previously showed that luminal glutamine is essential for optimal intestinal function. In this study, we examined the effect of apical vs basolateral glutamine on bacterial translocation in a Caco-2 cell culture system and bacteria-induced tissue injury in a weanling rabbit ileal loop model. METHODS: Caco-2 cells were grown in a transwell system. After confluence, apical and basolateral chambers received defined media, and glutamine deprivation was carried out over a 4- to 48-hour period. Escherichia coli transcytosis and structure/function studies were then performed. In a second series of experiments, the effect of intraluminal glutamine supplementation was evaluated in an E. coli-induced tissue injury model in weanling rabbit ileal loops. RESULTS: Expression of disaccharidases, glucoamylase, and Na+/K(+)-adenosine 5'-triphosphatase (ATPase) were significantly reduced when cells were deprived of glutamine from the apical side, and there was increased bacterial translocation across the monolayer. Transepithelial epithelial resistance (TEER) across the monolayer was also reduced in the glutamine-free cultures. Glutamine replenishment over 24 to 48 hours restored the original functions. Basolateral deprivation had a smaller effect on the Caco-2 cells. Typical necrotic mucosal injury caused by E. coli in the ileal loops was blocked by co-infiltration of the loops with glutamine. CONCLUSIONS: This study demonstrates for the first time that the supply of glutamine from the apical side is of critical importance for maintaining optimal structure and function of the enterocytes. The effects are not acute or energy related. These observations have important clinical implications in the management of patients under critical care, including premature infants and patients receiving TPN, for whom lack of glutamine from the luminal side could produce mucosal dysfunction, resulting ultimately in severe atrophic/necrotic complications.

Animals↗