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Splitting of Pi and other (31) P NMR anomalies of skeletal muscle metabolites in canine muscular dystrophy.

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Article

Wary, C. ; Naulet, T. ; Thibaud, Jean-Laurent ; Monnet, A. ; Blot, Stéphane ; Carlier, P.G.

NMR IN BIOMEDICINE

NMR Laboratory, Institute of Myology, Paris, France; CEA, I²BM, MIRCen, IdM NMR Laboratory, Paris, France; UPMC University Paris 06, Paris, France. c.wary@institut-myologie.org.

2012

Article

Volume : 25(10):1160-1169.

Abstract : Many anomalies exist in the resting (31) P muscle spectra of boys with Duchenne muscular dystrophy (DMD) but few have been reported in Golden Retriever muscular dystrophy (GRMD), the closest existing animal model for DMD. Because GRMD is recommended for preclinical evaluation of therapies and quantitative outcome measures are needed, we investigated anomalies of (31) P NMRS in tibial cranial and biceps femoris muscles from 14 GRMD compared to 9 control (CONT) dogs. Alterations observed in DMD children - low phosphocreatine and high phospho-monoesters and -diesters - were all found in GRMD but increased pH was not. More surprisingly, inorganic phosphate (Pi) appeared to present a prominent splitting with an enhanced Pi(b) resonance at 0.3?ppm downfield of Pi(a) . Assuming that both resonances are Pi, the pH for Pi(a) in GRMD corresponded to a physiological intracellular pH(a) (6.97?±?0.05), while pH(b) approached the extracellular range (7.27?±?0.10) and correlated with pH(a) in GRMD (R(2) ?=?0.65). Both Pi(a) and Pi(b) were elevated compared to CONT and Pi(a) increased with age for GRMD (R(2) ?=?0.48, p?
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