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Biomedical subjects

E V Cosmi

Publications and source records attributed to E V Cosmi.

At least 127 records · Page 7Linked to original sources

Fate of human albumin microsphere and spherocyte radioaerosols in the human tracheobronchial tree.

Human albumin microspheres (99mTc-HAM; 7-25 microns) and spherocytes (99mTc-S; 4-4.5 mu) are particles used for lung mucociliary clearance (MCC) measurements. If radiolabelled HAM aerosols are sent through an airway model to a screen, they appear peripherally distributed, whereas S present a more central and homogeneous distribution. The radioscanning evaluation of particle sedimentation in saline-filled tubes shows quite a different behavior pattern for S, HAM, and surfactant-coated HAM (S-C HAM). In these experimental conditions, S-C HAM and HAM floating properties were better than those of S. This could be explained by physical-chemical factors. Looking for the fate of organic particles after inhalation, we performed multiple bronchial biopsies in seven bronchitic patients, 2 h following inhalation of HAM and S. Scanning electron microscopy revealed that most of S was floating on the mucus layer, while HAM appeared deeply imbedded inside the mucus and partially digested. The same study performed on three bronchitic patients after S-C HAM inhalation, shows that S-C HAM float like S. In vitro, the time-course of tryptic digestion is similar for HAM and for S. However, in vivo, the different location of each particle on the bronchial surface might lead to a different digestion by trypsin and by PZ-peptidase, which are dosable in pathologic mucus. In our opinion, if HAM are coated with surfactant, this should improve the mucus-HAM interaction, thus helping to control variability in lung radioaerosol MCC studies.

Aerosols↗

CA 125 is released by human amnion cells in culture.

CA 125 was measured in the medium of human amnion cells in primary culture after confluence. The antigen accumulated as a function of time with a median value of 1897 U/mg protein after 7 days in culture. CA 125 was detectable by immunoperoxidase staining in the cells, which supports the possibility that amnion cells play a role as a source of the CA 125 found in the amniotic fluid.

Amnion↗

Multiple primer pairs polymerase chain reaction for the detection of human papillomavirus types.

A polymerase chain reaction (PCR) based on the use of multiple primers enabling the simultaneous detection of HPV-6b, -11, -16 and -18 in a single tube reaction was developed and validated on cervico-vaginal specimens, including tissues embedded in paraffin. This PCR setting proved to be specific and sensitive, allowing the detection of as few as 200 viral particles per specimen.

Base Sequence↗

Ontogeny of CA 125 antigen in pregnancy: immunoradiometric determination in amniotic fluid and immunohistochemical localization in fetal membranes.

CA 125 antigen was measured in amniotic fluid, maternal blood, cord blood, and fetal urine by a commercially available immunoradiometric assay kit. The amniotic fluid was obtained from 99 normal pregnancies at various gestational ages. The mean antigen levels were 29,676, 3350, and 1680 U/ml in amniotic fluid of the first, second, and third trimesters, respectively. In maternal blood, 12.5% of pregnant women in the first trimester of pregnancy showed elevated levels of CA 125 (65 to 100 U/ml). Late in gestation, CA 125 levels in cord blood and fetal urine were always less than 65 U/ml. Immunohistochemical study of CA 125 in fetal membranes, placenta, and decidua showed the presence of antigen only in the amnion. These results suggest that CA 125 is shed into amniotic fluid directly from the amniotic membrane.

Amniotic Fluid↗

Lung surfactant enhancement in utero.

Over the last 10 years the strategy for the prevention of neonatal respiratory distress syndrome (RDS) has been directed towards the acceleration of fetal lung maturity in utero by means of drugs administered to the mother, the most thoroughly investigated being glucocorticoids (GC). Many reports indicate that the administration of GC decreases the incidence of RDS in the neonate delivered between 28 and 32 weeks and weighing less than 1500 g. The type of GC and the drug-delivery interval are critical. Harmful potential side effects of GC have led to the testing of other drugs capable of accelerating fetal lung maturity, among them ambroxol and aminophylline. Ambroxol has been shown to reduce significantly RDS compared to placebo, without causing important adverse effects either on the mother or the baby. Our experimental studies on aminophylline have shown that the drug exerts only minor beneficial effects on fetal lung maturation and surfactant production. Recently we have evaluated the association of GC with inositol. The sugar alcohol dramatically affected pregnant rabbit fetal lung mechanisms, reducing GC-adverse effects such as decrease in lung DNA and protein content. In attempts to minimize the risk of neonatal RDS it is important (1) to identify pregnant women at risk for preterm labor; (2) to establish specific guidelines for the use of any prenatal drug to be administered for the prevention of RDS; (3) to assess fetal lung maturity; (4) to intensively monitor the fetus intrapartum; and (5) to prevent birth asphyxia.

Animals↗

Prevention and treatment of fetal lung immaturity.

In the last 10 years the strategy for the prevention of neonatal respiratory distress syndrome (RDS) has been directed towards the acceleration of fetal lung maturity in utero by means of drugs administered to the mother, the most thoroughly investigated being glucocorticoids (GC), and to the development of surfactant substitutes for the treatment of surfactant deficiency at birth or following the development of RDS. GC decreases the incidence of RDS in the neonate delivered between 28 and 32 weeks and weighing less than 1,500 g. The type of GC and the drug-delivery interval are critical. Harmful potential side effects of GC have led to the testing of other drugs capable of accelerating fetal lung maturity, among which are ambroxol and aminophylline. Ambroxol has been shown to significantly reduce RDS compared to placebo without causing important adverse effects in either mother or baby. Our experimental studies on aminophylline have shown that the drug exerts only minor beneficial effects on fetal lung maturation and surfactant production. We have evaluated the association of GC with inositol. The sugar alcohol administered to the mother dramatically affected fetal lung mechanics, reducing GC adverse effects such as the decrease of lung protein content. More recently supplementary surfactant instilled into the trachea has been shown to improve oxygenation of premature babies and to reduce the severity of RDS.

Adrenergic beta-Agonists↗

Assessment of foetal lung maturity.

An important prerequisite for the management of high risk pregnancies is the accurate prediction of foetal lung maturity. A number of indices of foetal lung maturity based on the determination of surfactant constituents in the amniotic fluid have been proposed. Amniotic fluid contains phospholipids, including phosphatidylcholine (lecithin), sphingomyelin, phosphatidylinositol and phosphatidylglyerol (PG), some enzymes of the pathways of phospholipid synthesis, lamellar bodies, and lung specific apoproteins. The amount of these substances in amniotic fluid changes towards the end of gestation in a manner related to foetal lung maturity. Determination of the lecithin to sphingomyelin (L/S) ratio is by far the most widely used and accepted method. However, there is still controversy regarding the high incidence of false immature values, and the increased incidence of false mature values (from 1 to 15%) especially in pregnancies complicated by diabetes mellitus; an immature L/S ratio may predict respiratory distress syndrome (RDS) only in about 50% of cases. The incidence of false immature L/S ratio as well as other amniotic fluid tests depends upon patient variability, method employed, threshold taken for differentiating a normal from an abnormal condition, and on the fact that only few authors report their results in terms of sensitivity and specificity. Where laboratory facilities are minimal, it is advisable to perform the shake test or to measure the optical density of amniotic fluid. However, when these tests indicate immaturity, additional tests, such as determination of the L/S ratio or the lung profile (including PG), must be performed. The utilization of these tests is recommended for: 1) timing of delivery prior to elective caesarean section; 2) management of complicated pregnancies; and 3) recognizing indications for pharmacologic prevention of RDS in utero or at delivery.

Amniotic Fluid↗

Requirements of perinatal prevention and treatment of respiratory distress syndrome.

In the last decade the strategy for the prevention of the neonatal respiratory distress syndrome (RDS) has been directed towards the acceleration of foetal lung maturation in utero by means of drugs administered to the mother, the most thoroughly investigated being glucocorticoids. Harmful potential side effects of glucocorticoids have led to testing of other drugs capable of accelerating foetal lung maturation, including ambroxol and aminophylline. More recently supplementary surfactant instilled into the trachea has been shown to improve oxygenation of premature babies and to reduce the severity of RDS. To minimise the incidence of neonatal RDS it is important to identify pregnant women at risk for preterm labour and to establish specific guidelines for the use of any prenatal drug to be administered for prevention of RDS. It is also mandatory to assess foetal lung maturity in case of preterm delivery, to monitor the foetus intensively intrapartum, to prevent birth asphyxia and to control, and promptly correct derangements of neonatal homeostasis.

Ambroxol↗

Inositol and glucocorticoid in the development of lung stability in male and female rabbit fetuses.

Inasmuch as inositol affects the development of lung surfactant, and exogenous glucocorticoids accelerate fetal lung maturation, a possible interaction of the two substances on alveolar stability of preterm rabbit fetuses of 28 days gestation was investigated. On days 26 and 27 of gestation inositol or glucose were added to the diet of does treated with betamethasone (0.2 mg/kg intramuscularly on days 26 and 27). Inositol increased lung-thorax compliance of paralyzed fetuses at all insufflation pressures studied (from 16 to 22.5 and 30 cm H2O and back to 22.5, and 16 cm H2O). At a ventilation pressure of 30 cm H2O, lung-thorax compliance of fetuses treated with inositol plus betamethasone was more than doubled as compared with controls (1.2 +/- 0.6 versus 0.5 +/- 0.2 ml/kg x cm H2O; p less than 0.001). Inositol alone had no detectable effect on compliance, whereas betamethasone tended to increase compliance (p = 0.05). According to variance analysis, the effect of inositol was statistically significant only among the males. Inositol prevented the glucocorticoid-induced decrease in lung protein and, to a lesser extent, the decrease in DNA. Inositol did not further increase the lavageable surfactant pool of the glucocorticoid-treated, ventilated fetuses, although the area occupied by lamellar bodies within type II cells was increased after inositol plus betamethasone. According to the present study, inositol modifies the physiologic and biochemical response of the immature fetal lung to a pharmacologic dose of exogenous glucocorticoid.

Animals↗

Alkaline phosphatase expression in human chorionic villi.

The physicochemical properties and electrophoretic mobility of different isoforms of alkaline phosphatase were studied in chorionic villi. Based on selective inactivation and inhibition studies (thermal stability, inactivation by urea, EDTA and L(+)ascorbic acid and L-amino acid inhibition), evidence was obtained for the existence of two distinct types of alkaline phosphatase in trophoblast cells. One type is peculiar to chorionic villi while the other is also found in term placenta. Both show two isoforms. These two isoforms were observed with polyacrylamide gel electrophoresis, carried out at pH 6.0 and 9.5. It is suggested that the qualitative and quantitative methods of alkaline phosphatase analysis could be used for first trimester fetal diagnosis of severe infantile hypophosphatasia and for understanding genetic control during early fetal development.

Alkaline Phosphatase↗

beta-N-acetyl-D-glucosaminidase isoenzymes from human amnionic membranes.

Two beta-N-acetylglucosaminidase isoenzymes (A and B) have been identified and purified from amnionic fetal membrane. The final specific activity of A and B isoenzymes increased 225- and 185-fold respectively by a purification scheme, which included a lyophilized extract, chromatofocusing on PBE 94, pH range 5.5 to 4.0, and affinity chromatography on p-aminophenyl-2-acetamido-2-deoxy-1-thio-beta-D-glucopyranoside covalently linked to Sepharose-4B. Different electrophoretic mobility, thermostability and different thiol group modifications of the two isoenzymes were found. Acetate was a more effective competitive inhibitor than were iodoacetamide, N-acetylglucosamine and N-acetylgalactosamine more than glucosamine and galactosamine, confirming a specific 'acetamido receptor site' for both the isoenzymes.

Acetylglucosaminidase↗

Effect of aminophylline on lung maturation in preterm rabbit fetuses.

Pregnant rabbit does were treated intravenously with aminophylline (6 mg/kg/day) from the twenty-fifth day after the day of mating, and the fetuses were delivered by hysterotomy on the twenty-eighth day. One group of neonates was breathing air, and another group 100% oxygen. Lung mechanics were evaluated in the newborn animals during spontaneous or artificial ventilation, and the lungs were studied histologically with particular reference to the alveolar volume density. In one series of experiments, the lungs were washed and the lavage fluid was analyzed for phosphatidylcholine and phosphatidylglycerol. Aminophylline-treated litters had greater body weights, an improved survival rate, and an increased amount of phosphatidylglycerol in lung lavage fluid. Respiratory frequency was increased in aminophylline-treated animals breathing air, but data on lung compliance showed no significant difference between treated and control animals. In the present model, the beneficial effect of aminophylline can be attributed largely to a combination of accelerated fetal growth and improved postnatal regulation of breathing and less to a specific influence on the biochemical and functional maturation of the lung.

Aminophylline↗

Improved lung-thorax compliance in the premature rabbit neonate after treatment with dibuturyladenosine-3':5'-cyclic monophosphate.

Premature rabbit neonates, delivered on day 28 of gestation, were treated with a single dose of dibuturyladenosine-3':5'-cyclic monophosphate (cyclic AMP), 300 mg/kg, immediately after delivery, saline-injected litter-mates serving as controls. All animals were kept in body plethysmographs and ventilated artificially with 100% oxygen for 1 h, with a maximal tidal volume of 10 ml/kg body weight. Lung-thorax compliance was significantly improved in animals treated with cyclic AMP, both 30 and 60 min after onset of ventilation (0.92 +/- 0.09 vs. 0.59 +/- 0.08 ml/cm H2O.kg and 0.96 +/- 0.09 vs. 0.53 +/- 0.08, p less than 0.005), but there was no improvement in alveolar air expansion, evaluated histologically. Phosphatidylglycerol was absent in alveolar wash from all control animals, but present in 3 of the 8 pooled samples from the animals treated with cyclic AMP; this difference was not statistically significant, however.

Animals↗

Opioid plasma levels during labour.

6 healthy pregnant women, monitored with external cardiotocography, were studied. Blood samples were collected hourly throughout labour until delivery of the fetus and placenta, and again on the 5th day of puerperium. beta-Lipotropin (beta LPH) and beta-endorphin (beta EP) were determined by specific radioimmunoassays in each sample, after silicic acid plasma extraction and G-75 column chromatography. Both opioid plasma levels rise progressively during labour, reaching their highest values 1 h before delivery (beta LPH: 296.0 +/- 60.2 pg/ml; beta EP 106.2 +/- 40.6 pg/ml) as compared with values of 157.0 +/- 35.4 (beta LPH) and 57.0 +/- 7.3 pg/ml (beta EP) (mean +/- SE) at the beginning of labour. With the exception of 1 case, a significant correlation was observed between beta LPH and beta EP plasma levels. The two opioid plasma levels decrease after delivery of the placenta (272.5 +/- 59.6 and 118.2 +/- 68.4 pg/ml) and subsequently decrease further to levels of 105.6 +/- 46.4 (beta LPH) and 33.7 +/- 16.5 (beta RP) on the 5th day of puerperium. beta LPH and beta EP plasma levels showed a significant correlation throughout labour with the 'uterine contractility force/hour', which was calculated by the addition of tocographic areas of each uterine contraction at 1-hour intervals. These data demonstrate that the increase in plasma opioid concentrations during labor is directly related to the number and intensity of uterine contractions.

Endorphins↗

The in vitro inhibitory effect on thrombin by 2,3-diphosphoglycerate.

Thrombin incubated with 2,3-diphosphoglycerate (150 nmol 2,3-DPG/1 NIH thrombin unit) lost up to 70% of its clotting activity, whereas the esterase activity remained unchanged. No fibrinopeptide release by thrombin was observed in the presence of 2,3-DPG. The fibrin polymerization was normal. By chromatography on Amberlite IRC-50, alpha-thrombin was eluted at pH 8.0. In presence of 2,3-DPG, alpha-thrombin was not eluted. Likely, 2,3-DPG can interfere with thrombin.

Animals↗