scholarly journals Altered Metabolic Profile in Congenital Lung Lesions Revealed by 1H Nuclear Magnetic Resonance Spectroscopy

2014 ◽  
Vol 2014 ◽  
pp. 1-8 ◽  
Author(s):  
Maria Chiara Mimmi ◽  
Maurizio Ballico ◽  
Ghassan Nakib ◽  
Valeria Calcaterra ◽  
Jose Louis Peiro ◽  
...  

Congenital lung lesions are highly complex with respect to pathogenesis and treatment. Large-scale analytical methods, like metabolomics, are now available to identify biomarkers of pathological phenotypes and to facilitate clinical management. Nuclear magnetic resonance (NMR) is a unique tool for translational research, as in vitro results can be potentially translated into in vivo magnetic resonance protocols. Three surgical biopsies, from congenital lung malformations, were analyzed in comparison with one control sample. Extracted hydrophilic metabolites were submitted to high resolution 1H NMR spectroscopy and the relative concentration of 12 metabolites was estimated. In addition, two-dimensional NMR measurements were performed to complement the results obtained from standard monodimensional experiments. This is one of the first reports of in vitro metabolic profiling of congenital lung malformation. Preliminary data on a small set of samples highlights some altered metabolic ratios, dealing with the glucose conversion to lactate, to the relative concentration of phosphatidylcholine precursors, and to the presence of myoinositol. Interestingly some relations between congenital lung lesions and cancer metabolic alterations are found.

Author(s):  
O. Kaplan ◽  
J.S. Cohen

Nuclear magnetic resonance spectroscopy (NMR) is a powerful technique that provides information on biochemical status and physiological processes both in-vitro and in-vivo. The metabolism of intact cells and tissues can be studied in a continuous manner, and thus, NMR is a unique non-invasive research tool enabling detection of the metabolic changes as they occur (Cohen et al., 1983; Morris, 1988; Daly and Cohen, 1989). The first NMR study of cellular metabolism was done some 20 years ago, when Moon and Richards reported on the diphosphoglyceric acid (DPG) and pH shifts in erythrocytes (Moon, and Richards, 1973). NMR studies of metabolism of tumor cells were initiated by Navon et al. who investigated phosphorylated compounds in Ehrlich ascites cells (Navon etal., 1977). The choice of the element and isotope for a specific study of metabolism depends on its NMR properties, and the required data. The proton has the highest NMR sensitivity, and is the most abundant nucleus in biological molecules. However, this may cause difficulties in the interpretation and assignment of the 1H NMR spectrum. Moreover, since metabolic studies are usually performed in aqueous solutions, the huge signal from the water protons should be suppressed. Similarly, the wide signals arising from proteins and membrane components should be suppressed. These problems can be addressed now by several innovative NMR methods (Daniels et al., 1976; van Zijl and Cohen, 1992). The most widely used nucleus in NMR studies of metabolism has been 31p (see reviews Cohen (1988); Kaplan et al. (1992)). Phosphorous NMR spectroscopy can provide data on energy metabolism and substrate utilization, phospholipid pathways, precise intracellular pH, and membrane permeability and ion and water distribution. The spectrum is easy to interpret, but the number of compounds which are detectable is limited. Carbon NMR is also useful for NMR studies of metabolism since it is found in most biological compounds; however, 13C has a natural abundance of only 1.1%, and 13C enrichment is necessary. Other nuclei which are used less often in NMR studies of cellular metabolism are 23Na (Gupta et al., 1984), 19F (Malet-Martino, et al., 1986), and rarely 15N (Legerton et al., 1983) and 39K (Brophy et al., 1983).


2000 ◽  
Vol 66 (5) ◽  
pp. 2012-2020 ◽  
Author(s):  
Catherine Deborde ◽  
Patrick Boyaval

ABSTRACT In vivo 13C nuclear magnetic resonance spectroscopy was used to elucidate the pathways and the regulation of pyruvate metabolism and pyruvate-lactate cometabolism noninvasively in living-cell suspensions of Propionibacterium freudenreichiisubsp. shermanii. The most important result of this work concerns the modification of fluxes of pyruvate metabolism induced by the presence of lactate. Pyruvate was temporarily converted to lactate and alanine; the flux to acetate synthesis was maintained, but the flux to propionate synthesis was increased; and the reverse flux of the first part of the Wood-Werkman cycle, up to acetate synthesis, was decreased. Pyruvate was consumed at apparent initial rates of 148 and 90 μmol · min−1 · g−1 (cell dry weight) when it was the sole substrate or cometabolized with lactate, respectively. Lactate was consumed at an apparent initial rate of 157 μmol · min−1 · g−1when it was cometabolized with pyruvate. P. shermanii used several pathways, namely, the Wood-Werkman cycle, synthesis of acetate and CO2, succinate synthesis, gluconeogenesis, the tricarboxylic acid cycle, and alanine synthesis, to manage its pyruvate pool sharply. In both types of experiments, acetate synthesis and the Wood-Werkman cycle were the metabolic pathways used most.


2019 ◽  
Vol 2019 ◽  
pp. 1-16
Author(s):  
Siwar Mosbahi ◽  
Hassane Oudadesse ◽  
Claire Roiland ◽  
Bertrand Lefeuvre ◽  
Lotfi Slimani ◽  
...  

The present study aimed to enhance the anti-osteoporotic performance of bioactive glass (46S6) through its association with bisphosphonate such as risedronate with amounts of 8, 12, and 20%. Obtained composites have been called 46S6-8RIS, 46S6-12RIS, and 46S6-20RIS, respectively. In vitro and in vivo explorations have been carried out. Bioactive glass and risedronate association has been performed by adsorption process. Structure analyses have been carried out to evaluate and to understand their chemical interactions. Solid Nuclear Magnetic Resonance (NMR) has been employed to study the structural properties of obtained biocomposite. The spectra deconvolution showed the appearance of a species (Q4) in the biocomposites 46S6-8RIS, 46S6-12RIS, and 46S6-20RIS indicating their successful chemical association. In vitro experiments showed the enhancement of the chemical reactivity of the composites 46S6-xRIS compared to the pure bioactive glass. In fact, the silicon liberation after 30 days of immersion was 50 ppm for pure bioactive glass 46S6, and 41, 64, and 62 from 46S6-8RIS, 46S6-12RIS, and 46S6-20RIS, respectively. Based on the in vitro results, 46S6-8RIS was implanted in the femoral condyle of an ovariectomized rat and compared with implanted pure glass in the goal to highlight its anti-osteoporotic performance. After 60 days, implanted group with 46S6-8RIS showed the increase in bone mineral density (BMD with 10%) and bone volume fraction (BV/TV with 80%) and the decrease in trabecular separation (Tb/Sp with 74%) when compared to that of 46S6 group. These results are confirmed by the histopathological analyses, which showed the bone trabeculae reconnection after the 46S6-8RIS implantation. Chemical analyses showed the reduction in silicon (Si) and sodium (Na) ion concentrations, and the rise in calcium (Ca) and phosphorus (P) ion levels, which was explained by the dissolution of biocomposite matrix and the deposition of hydroxyapatite layer. Histomorphometric results highlighted the risedronate effect on the antiosteoporotic phenomenon. Obtained results showed good behavior with only 8% of introduced risedronate in the glass matrix.


1995 ◽  
Vol 269 (2) ◽  
pp. C318-C322 ◽  
Author(s):  
S. K. Song ◽  
R. S. Hotchkiss ◽  
J. Neil ◽  
P. E. Morris ◽  
C. Y. Hsu ◽  
...  

Fluorine-19-nuclear magnetic resonance (19F-NMR) spectroscopic detection of the NMR-active Ca2+ indicator 5-fluoro-1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid (5F-BAPTA) is one method for measuring cytosolic free Ca2+ concentration ([Ca2+]i) and has been used previously to measure [Ca2+]i in isolated cells and perfused organs. The aim of the present investigation was to demonstrate the feasibility of determining [Ca2+]i in vivo and in situ using 19F-NMR and 5F-BAPTA. Experiments were performed on male Sprague-Dawley rats with a surface-coil antenna employed for NMR interrogation. The Ca2+ indicator, 5F-BAPTA, was infused either intravenously (kidney, spleen) or intraventricularly (brain) as a 100 mg/ml solution of the cell-permeant acetoxymethyl ester (5F-BAPTA-AM) in dimethyl sulfoxide. Rats tolerated intravenous infusion without evident change in mean arterial blood pressure. In all tissues examined, kidney, spleen, and brain, [Ca2+]i was approximately 200 nM. To our knowledge, these results represent the first in vivo and in situ determinations of [Ca2+]i employing 19F-NMR.


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