A new device combining mechanical stimulation of plantar sole and Achilles' tendon to alleviate the consequences of muscle deconditioning.

Limb immobilization or confinement to bed results in a severe atrophy and weakness of lower leg muscles. Full recovery of muscle strength and physical function is rare and may impact the patient's outcome. Studies performed on rodents have demonstrated that the deleterious structural and functional adaptations which occur during muscle deconditioning can be counteracted through adequate physiological stimuli. Thus, based on this fundamental work, we developed a device that combines mechanical stimulation of proprioceptors located in the plantar sole and Achilles' tendon. The device is adapted to patients immobilized and confined to bed. Stimulations can be applied on muscle in passive state. The protocol is non-invasive and is well accepted by patients. This paper presents the technical features of the device, as well as preliminary results of the first clinical study. This device might allow considering new therapeutic strategies for prevention of atrophy in many pathologies.

Conjugated linoleic acid isomers in mitochondria: evidence for an alteration of fatty acid oxidation.

The beneficial effects exerted by low amounts of conjugated linoleic acids (CLA) suggest that CLA are maximally conserved and raise the question about their mitochondrial oxidizability. Cis-9,trans-11-C(18:2) (CLA1) and trans-10,cis-12-C(18:2) (CLA2) were compared to cis-9,cis-12-C(18:2) (linoleic acid; LA) and cis-9-C(16:1) (palmitoleic acid; PA), as substrates for total fatty acid (FA) oxidation and for the enzymatic steps required for the entry of FA into rat liver mitochondria. Oxygen consumption rate was lowest when CLA1 was used as a substrate with that on CLA2 being intermediate between it and the respiration on LA and PA. The order of the radiolabeled FA oxidation rate was PA >> LA > CLA2 > CLA1. Transesterification to acylcarnitines of the octadecadienoic acids were similar, while uptake across inner membranes of CLA1 and, to a lesser extent, of CLA2 was greater than that of LA or PA. Prior oxidation of CLA1 or CLA2 made re-isolated mitochondria much less capable of oxidising PA or LA under carnitine-dependent conditions, but without altering the carnitine-independent oxidation of octanoic acid. Therefore, the CLA studied appeared to be both poorly oxidizable and capable of interfering with the oxidation of usual FA at a step close to the beginning of the beta-oxidative cycle.

High yield synthesis of tentoxin, a cyclic tetrapeptide.

Tentoxin is a naturally occurring phytotoxic cyclic tetrapeptide excreted by fungi of the Alternaria alternata family. The four total syntheses of tentoxin published to date give poor total yields, mainly owing to two difficulties, the introduction of the dehydro amino acid and more especially the cyclization step. Here we describe a method that stereospecifically introduces Z-dehydrophenylalanine (deltaZPhe) by a modified Erlenmeyer aldolization reaction. The linear tetrapeptide, Boc-R1Ala-Leu-R2deltaZPhe-G1y-OMe (R1, R2: CH3, 14CH3), the precursor of tentoxin, was obtained in a 72% yield from Boc-Leu-Gly-OH. This linear tetrapeptide, labelled with carbon-14, was used for a comparative study of four cyclization reagents DPPA, DCC-PfpOH, HBTU and HATU. This last was the most effective and gave tentoxin in a 81% cyclization yield. The activated ester formed with this reagent displayed an enhanced capacity for cyclization, permitting cyclization in concentrated medium (10 mM). This new synthetic route gave tentoxin in a 60% yield from Boc-Leu-Gly-OH and offers a means of achieving the synthesis of hitherto elusive analogues.