scholarly journals Metabolomic profile of amniotic fluid to evaluate lung maturity: the diaphragmatic hernia lamb model

2014 ◽  
Vol 9 ◽  
Author(s):  
Gloria Pelizzo ◽  
Maurizio Ballico ◽  
Maria Chiara Mimmi ◽  
José Louis Peirò ◽  
Mario Marotta ◽  
...  
Keyword(s):  
Amniotic Fluid ◽  
Diaphragmatic Hernia ◽  
Control Group ◽  
Metabolomic Profile ◽  
Lung Maturation ◽  
Metabolomic Profiling ◽  
Gestation Age ◽  
Alveolar Tissue ◽  
Global Growth ◽  
Lung Maturity

Background: Tracheal occlusion (TO) stimulates lung growth in fetuses affected with congenital diaphragmatic hernia (CDH) although the processes involved in lung maturation still remain unknown. The objective of this study was to evaluate the metabolomic profile of amniotic fluid (AF) following TO in fetal lamb model in order to obtain an indirect view of mechanisms involved in pulmonary reversal hypoplasia and biochemical maturity in response to fetal TO. Methods: Liquid Chromatography Mass Spectrometry was performed on lamb AF samples at: age I (70 days’gestation); age II (102 days’ gestation); age III (136 days’ gestation). CDH was induced at age I and TO at age II. Results: Betaine, choline, creatinine were found significantly increased during gestation in the control group. The CDH group showed choline (p =0.007) and creatinine (p =0.004) decreases during pregnancy. In the TO group choline and creatinine profiles were restored. Conclusions: Alveolar tissue and fetal global growth ameliorated after TO. Metabolomics provided useful information on biochemical details during lung maturation. Metabolomic profiling would help to identify the best time to perform TO, in order to increase survival of CDH affected patients.

scholarly journals Metabolomic profile of amniotic fluid to evaluate lung maturity: the diaphragmatic hernia lamb model

2014 ◽  
Vol 9 (1) ◽  
Author(s):  
Gloria Pelizzo ◽  
Maurizio Ballico ◽  
Maria Chiara Mimmi ◽  
José Louis Peirò ◽  
Mario Marotta ◽  
...  
Keyword(s):  
Amniotic Fluid ◽  
Diaphragmatic Hernia ◽  
Metabolomic Profile ◽  
Lung Maturity

Congenital diaphragmatic hernia: endotracheal fluid phospholipidic profile following tracheal occlusion in an experimental model

2017 ◽  
Vol 45 (2) ◽  
Author(s):  
Gloria Pelizzo ◽  
Maria Chiara Mimmi ◽  
Jose Luis Peiro ◽  
Mario Marotta ◽  
Francesco Amoroso ◽  
...  
Keyword(s):  
Congenital Diaphragmatic Hernia ◽  
Diaphragmatic Hernia ◽  
Partial Recovery ◽  
Lung Maturation ◽  
Tracheal Occlusion ◽  
Dipalmitoyl Phosphatidylcholine ◽  
Recovery Profile ◽  
Profile Changes ◽  
Lung Maturity

AbstractObjective:To compare endotracheal fluid (EF) and amniotic fluid (AF) phospholipidic profile changes following tracheal occlusion (TO) in the congenital diaphragmatic hernia (CDH) fetal lamb model, in order to support the efficacy of TO on lung maturity.Methods:A diaphragmatic defect was induced at 70 days’ gestation, TO was carried out at day 102 and cesarean section at 136 days’ gestation. EF and AF samples, collected at delivery, were evaluated using mass spectrometry (the analysis focused on palmitoyloleoyl-phosphatidylcholine [POPC, PC(18:1/16:0)], dipalmitoyl-phosphatidylcholine [DPPC, PC(16:0/16:0)] and sphingomyelins [SMs]).Results:The effects of CDH and TO were different on AF and EF. POPC levels were higher than DPPC levels in AF of healthy lambs. Following induction of the diaphragmatic malformation, an evident decrease in POPC was noted, while a substantial return to normal POPC levels and an increased DPPC peak were prompted by the TO. After CDH induction, a decrease in N-palmitoyl-D-sphingomyelin [SM(d18:1/16:0)] was revealed (P<0.01) and an increased peak in SMs in AF was prompted by the TO (P=0.05). While the most represented phosphatidylcholine (PC) species in EF of healthy lambs was DPPC, CDH induced a decrease in the DPPC peak and treatment with TO induced its partial recovery. SMs were detectable only in healthy EF samples.Conclusion:The phospholipid recovery profile following TO suggests the potential role of this therapy in restoring processes involved in surfactant-mediated lung maturation, even though other interactions involved in AF turnover should be considered. Moreover, these metabolites could be used as biomarkers of fetal pulmonary development.

Fetal lung maturation in diabetic pregnancy

1986 ◽  
Vol 113 (3_Suppl) ◽  
pp. S101-S106 ◽  
Author(s):  
Olof Tydén ◽  
Ulf J. Eriksson ◽  
Christian Berne
Keyword(s):  
Amniotic Fluid ◽  
Metabolic Control ◽  
Preterm Delivery ◽  
Experimental Studies ◽  
Fetal Lung ◽  
Diabetic Pregnancy ◽  
Phosphatidyl Glycerol ◽  
Lung Maturation ◽  
Metabolic Derangement ◽  
Lung Maturity

Abstract. The increased incidence of the idiopathic respiratory distress syndrome (IRDS) in infants of diabetic mothers may be explained by preterm delivery and asphyxia but the metabolic derangement per se may also be responsible for the inadequate production of surfactant. Experimental studies of the underlying mechanisms in the lungs of fetuses of pregnant diabetic rats have shown a decreased formation of the two major surfactant phospholipids disaturated phosphatidyl choline and phosphatidyl glycerol. In addition, the activities of key enzymes responsible for the production of these phospholipids are decreased in the fetal lung tissue. Inadequate utilization of pulmonary glycogen for surfactant biosynthesis has also been observed. Furthermore, experimental studies support that other changes than fetal hyperinsulinaemia are needed to produce a state of disturbed surfactant production. In human diabetic pregnancy strict metabolic control allows the fetal lungs to mature in a near-normal fashion. The presence of phosphatidyl glycerol in the amniotic fluid seems to be the best available predictor of lung maturity in diabetic pregnancy, in which both the lecithin/sphingomyelin ratio and amniotic fluid cytology may result in false-positive and false-negative values. The trend towards extension of delivery to term will undoubtedly diminish the need for estimation of fetal lung maturity by amniocentesis. Avoiding preterm delivery and adhering to strict metabolic control of the maternal diabetes would be expected to decrease the neonatal respiratory problems in diabetic pregnancy.

Fetal lung maturity in complicated pregnancy, as predicted from microviscosity of amniotic fluid.

1982 ◽  
Vol 28 (8) ◽  
pp. 1754-1757 ◽  
Author(s):  
N V Simon ◽  
W A Hohman ◽  
R C Elser ◽  
J S Levisky ◽  
M J Carp ◽  
...  
Keyword(s):  
Amniotic Fluid ◽  
Fetal Lung ◽  
Hyaline Membrane Disease ◽  
Lung Maturation ◽  
Class D ◽  
Hyaline Membrane ◽  
Induced Hypertension ◽  
Complicated Pregnancy ◽  
Fetal Lung Maturation ◽  
Lung Maturity

Abstract We measured the microviscosity of amniotic fluid between 28 and 40 weeks of gestation in 252 normal pregnancies and in 172 pregnancies complicated by factors known to influence fetal lung maturation, including chronic high blood pressure, pregnancy-induced hypertension, diabetes mellitus, and therapy with betamethasone. Comparison of the microviscosity value distributions and regression analysis indicated significantly lower microviscosity values in hypertensive disorders, in Class D and Classes F or R diabetes, and after 48 h of treatment with betamethasone. Few changes were observed in Classes A, B, or C diabetes. These observations are consistent with the accelerated maturation of surfactant observed in chronic intrauterine stress and the lower incidence of hyaline membrane disease reported after glucocorticoids.

scholarly journals A Plasma Metabolomic Profiling of Exudative Age-Related Macular Degeneration Showing Carnosine and Mitochondrial Deficiencies

2020 ◽  
Vol 9 (3) ◽  
pp. 631 ◽  
Author(s):  
Juan M. Chao de la Barca ◽  
Barnabé Rondet-Courbis ◽  
Marc Ferré ◽  
Jeanne Muller ◽  
Adrien Buisset ◽  
...  
Keyword(s):  
Macular Degeneration ◽  
Age Related Macular Degeneration ◽  
Control Group ◽  
P Value ◽  
Metabolomic Profile ◽  
Exudative Amd ◽  
Metabolomic Profiling ◽  
Age Related ◽  
Metabolomics Study ◽  
Anti Oxidant

To determine the plasma metabolomic profile of exudative age-related macular degeneration (AMD), we performed a targeted metabolomics study on the plasma from patients (n = 40, mean age = 81.1) compared to an age- and sex-matched control group (n = 40, mean age = 81.8). All included patients had documented exudative AMD, causing significant visual loss (mean logMAR visual acuity = 0.63), compared to the control group. Patients and controls did not differ in terms of body mass index and co-morbidities. Among the 188 metabolites analyzed, 150 (79.8%) were accurately measured. The concentrations of 18 metabolites were significantly modified in the AMD group, but only six of them remained significantly different after Benjamini–Hochberg correction. Valine, lysine, carnitine, valerylcarnitine and proline were increased, while carnosine, a dipeptide disclosing anti-oxidant and anti-glycating properties, was, on average, reduced by 50% in AMD compared to controls. Moreover, carnosine was undetectable for 49% of AMD patients compared to 18% in the control group (p-value = 0.0035). Carnitine is involved in the transfer of fatty acids within the mitochondria; proline, lysine and valerylcarnitine are substrates for mitochondrial electrons transferring flavoproteins, and proline is one of the main metabolites supplying energy to the retina. Overall, our results reveal six new metabolites involved in the plasma metabolomic profile of exudative AMD, suggesting mitochondrial energetic impairments and carnosine deficiency.

scholarly journals Metabolic Evaluation of Urine from Patients Diagnosed with High Grade (HG) Bladder Cancer by SPME-LC-MS Method

Molecules ◽  
2021 ◽  
Vol 26 (8) ◽  
pp. 2194
Author(s):  
Kamil Łuczykowski ◽  
Natalia Warmuzińska ◽  
Sylwia Operacz ◽  
Iga Stryjak ◽  
Joanna Bogusiewicz ◽  
...  
Keyword(s):  
Thin Film ◽  
Bladder Cancer ◽  
High Performance ◽  
Biomarker Discovery ◽  
Solid Phase ◽  
Biological Fluids ◽  
Reversed Phase ◽  
Control Group ◽  
Metabolic Evaluation ◽  
Metabolomic Profiling

Bladder cancer (BC) is a common malignancy of the urinary system and a leading cause of death worldwide. In this work, untargeted metabolomic profiling of biological fluids is presented as a non-invasive tool for bladder cancer biomarker discovery as a first step towards developing superior methods for detection, treatment, and prevention well as to further our current understanding of this disease. In this study, urine samples from 24 healthy volunteers and 24 BC patients were subjected to metabolomic profiling using high throughput solid-phase microextraction (SPME) in thin-film format and reversed-phase high-performance liquid chromatography coupled with a Q Exactive Focus Orbitrap mass spectrometer. The chemometric analysis enabled the selection of metabolites contributing to the observed separation of BC patients from the control group. Relevant differences were demonstrated for phenylalanine metabolism compounds, i.e., benzoic acid, hippuric acid, and 4-hydroxycinnamic acid. Furthermore, compounds involved in the metabolism of histidine, beta-alanine, and glycerophospholipids were also identified. Thin-film SPME can be efficiently used as an alternative approach to other traditional urine sample preparation methods, demonstrating the SPME technique as a simple and efficient tool for urinary metabolomics research. Moreover, this study’s results may support a better understanding of bladder cancer development and progression mechanisms.

scholarly journals Changes on proteomic and metabolomic profile in serum of mice induced by chronic exposure to tramadol

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Shukun Jiang ◽  
Guojie Liu ◽  
Huiya Yuan ◽  
Enyu Xu ◽  
Wei Xia ◽  
...  
Keyword(s):  
Chronic Exposure ◽  
Molecular Mechanisms ◽  
Fatty Acid Biosynthesis ◽  
Serum Proteins ◽  
Enzyme Inhibitor ◽  
Bile Secretion ◽  
Control Group ◽  
Protein Digestion ◽  
Metabolomic Profile ◽  
Apolipoprotein C

AbstractTramadol is an opioid used as an analgesic for treating moderate or severe pain. The long-term use of tramadol can induce several adverse effects. The toxicological mechanism of tramadol abuse is unclear. Limited literature available indicates the change of proteomic profile after chronic exposure to tramadol. In this study, we analyzed the proteomic and metabolomic profile by TMT-labeled quantitative proteomics and untargeted metabolomics between the tramadol and the control group. Proteomic analysis revealed 31 differential expressed serum proteins (9 increased and 22 decreased) in tramadol-treated mice (oral, 50 mg/kg, 5 weeks) as compared with the control ones. Bioinformatics analysis showed that the dysregulated proteins mainly included: enzyme inhibitor-associated proteins (i.e. apolipoprotein C-III (Apoc-III), alpha-1-antitrypsin 1–2 (Serpina 1b), apolipoprotein C-II (Apoc-II), plasma protease C1 inhibitor, inter-alpha-trypsin inhibitor heavy chain H3 (itih3)); mitochondria-related proteins (i.e. 14-3-3 protein zeta/delta (YWHAZ)); cytoskeleton proteins (i.e. tubulin alpha-4A chain (TUBA4A), vinculin (Vcl)). And we found that the differential expressed proteins mainly involved in the pathway of the protein digestion and absorption. Metabolomics analysis revealed that differential expressed metabolites mainly involved in protein ingestion and absorption, fatty acid biosynthesis, steroid hormone biosynthesis and bile secretion. Our overall findings revealed that chronic exposure to tramadol changed the proteomic and metabolomic profile of mice. Moreover, integrated proteomic and metabolomic revealed that the protein digestion and absorption is the common enrichment KEGG pathway. Thus, the combination of proteomics and metabolomics opens new avenues for the research of the molecular mechanisms of tramadol toxicity.

scholarly journals LB20. Valacyclovir to Prevent Vertical Transmission of Cytomegalovirus After Maternal Primary Infection During Pregnancy

2019 ◽  
Vol 6 (Supplement_2) ◽  
pp. S1002-S1002 ◽  
Author(s):  
Keren Shahar-Nissan ◽  
Joseph Pardo ◽  
Orit Peled ◽  
Irit Krause ◽  
Efraim Bilavsky ◽  
...  
Keyword(s):  
Amniotic Fluid ◽  
Vertical Transmission ◽  
Primary Infection ◽  
Antiviral Drug ◽  
First Trimester ◽  
Controlled Study ◽  
Therapeutic Drug ◽  
Control Group ◽  
Cmv Infection ◽  
In Pregnancy

Abstract Background Cytomegalovirus (CMV) is the most common cause of congenital infection in humans. The highest risk of fetal injury follows a maternal primary infection early in pregnancy. Despite the potential for severe fetal injury, to date there are no proven means to prevent viral transmission. Valacyclovir is an antiviral drug proven effective in decreasing the risk for CMV infection among transplant recipients. Valacyclovir is safe for use in pregnancy, and concentrates in the amniotic fluid without accumulating. A dose of 8 g/day creates therapeutic drug levels in the amniotic fluid and fetal blood. Methods This is a randomized, double-blind, placebo-controlled study comprising pregnant women with serologic evidence of primary CMV infection during the periconceptional period and first trimester. After informed consent, patients were randomly assigned to a treatment group (8 g/day of Valacyclovir) or control group (placebo). Treatment was initiated at the time of serological detection, and continued until amniocentesis. The primary endpoint was the rate of vertical transmission of CMV—determined by amniotic fluid CMV PCR. Secondary endpoints included evidence of symptomatic congenital CMV infection—in utero or postnatally. Results One hundred women were recruited, 90 were included in the data analysis; 45 patients received Valacyclovir and 45 placebo. There were 2 twin pregnancies, and therefore 92 amniocentesis Amongst the Valacyclovir group, 5 (11.1%) amniocentesis were positive for CMV, compared with 14 (29.8%) in the placebo group (P GLMM = 0.03), corresponding with an odds ratio of 0.29 (95% CI: 0.09–0.90) for vertical CMV transmission. Amongst patients infected during the first trimester, a positive amniocentesis for CMV was significantly (P = 0.02) less likely in the Valacyclovir arm (2/19) compared with placebo (11/23). No significant differences (P = 0.91) in CMV-positive amniocentesis were observed between study arms amongst patients infected periconceptionally. Conclusion Valacyclovir at a dose of 8 g/day is effective in reducing the rate of fetal CMV infection following early maternal primary infection during pregnancy. The drug reduces the rate of fetal infection by 71%. Disclosures All authors: No reported disclosures.

Improved thin-layer chromatography of disaturated phosphatidylcholine in amniotic fluid.

1981 ◽  
Vol 27 (2) ◽  
pp. 239-242 ◽  
Author(s):  
M Y Tsai ◽  
M Cain ◽  
M W Josephson
Keyword(s):  
Respiratory Distress ◽  
Thin Layer ◽  
Amniotic Fluid ◽  
Thin Layer Chromatography ◽  
Fetal Lung ◽  
Dipalmitoyl Phosphatidylcholine ◽  
Fetal Lung Maturity ◽  
Coefficients Of Variation ◽  
Layer Chromatography ◽  
Lung Maturity

Abstract We describe an indirect test of fetal lung maturity: the quantitation of disaturated phosphatidylcholine in amniotic fluid. The lipids in samples of amniotic fluid from 172 patients were reacted with osmium tetroxide, and disaturated phosphatidylcholine was then isolated by thin-layer chromatography. Interfering substances were retained by a pre-adsorbent layer. The charred disaturated phosphatidylcholine, quantitated by densitometry, was compared to standard dipalmitoyl phosphatidylcholine. Both within-run and between-run coefficients of variation were about 10%. Blood and meconium do not interfere. Six infants developed respiratory distress when disaturated phosphatidylcholine concentrations of amniotic fluid drawn within 72 h of delivery were less than 5.5 mg/L. A concurrently determined lecithin/sphingomyelin ratio falsely predicted lung maturity in one of these. In seven other samples for which lecithin/sphingomyelin ratios suggested lung immaturity but disaturated phosphatidyl-choline predicted maturity, none of the infants developed respiratory distress. In normal pregnancies, measurement of disaturated phosphatidylcholine in amniotic fluid appears to be a better predictor of fetal lung maturity than is measurement of the lecithin/sphingomyelin ratio. Further studies are needed to determine if this analysis is a better predictor in diabetic pregnancies.

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